三种氨基酸添加下酶法修饰酪蛋白水解物及其体外ACE抑制和抗氧化活性
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摘要
高血压是引发心血管疾病如心力衰竭、中风、冠心病和心肌梗塞的重要危险因素。高血压在发病前是没有任何征兆的,所以它十分危险。据统计,全世界每年因高血压引发的心脑血管疾病而死亡的人数超过1200万,高血压已经成为人类健康的第一杀手,成为全球性的重大公共卫生问题。近年来的研究结果表明,酪蛋白除具有一定的营养功能之外还具有重要的生理功能,是生物活性肽的重要来源。其中食物蛋白源ACE抑制肽安全性高、副作用小、易吸收,已经成为活性肽领域研究热点,这些ACE抑制肽在开发具有降血压功能的食品中具有广阔的应用前景。本研究在添加外源性氨基酸的情况下对酪蛋白水解物进行类蛋白反应修饰,以期得到高活性的肽。
利用Alcalase 2.4L FG蛋白酶水解酪蛋白,制备生物活性肽。酪蛋白水解物的ACE抑制活性最高值出现的水解时间为6h,其相应的水解度为12.4%、IC_(50)值为42.2μg/mL、DPPH自由基清除率为41.8%。酪蛋白水解物的ACE抑制活性和水解度之间有一定的关系:当酪蛋白水解物的水解度较低时,酪蛋白中具有ACE抑制活性的片段未被充分释放出来,导致酪蛋白水解物ACE抑制活性低;当酪蛋白水解物的水解度过高时,酪蛋白ACE抑制肽进一步酶解,从而失去它们的ACE抑制性。
利用中心组合设计和响应面分析法,优化类蛋白反应条件。固定酪蛋白水解物的浓度为35%(m/m),反应时间为6 h,以反应体系中游离氨基减少量为响应值,考察氨基酸添加量、酶添加量、反应温度及3种外源性氨基酸对类蛋白反应程度的影响。研究发现:(1)氨基酸添加量、反应温度、氨基酸种类对类蛋白反应的影响显著,而酶添加量对类蛋白反应的影响不大。(2)在分别添加亮氨酸、苯丙氨酸、缬氨酸后,同样研究反应条件对酪蛋白水解物进行类蛋白反应的影响,发现所得到研究结果是相似的。得到在3种外源性氨基酸添加下酪蛋白水解物类蛋白反应的最适反应条件为:氨基酸添加量0.6 mol/mol、酶添加量3 kU/g蛋白、反应温度40℃;(3)对类蛋白反应影响的最主要因素为氨基酸添加量、反应温度。
分别添加苯丙氨酸、亮氨酸、缬氨酸于酪蛋白水解物进行类蛋白反应,制备3个酪蛋白水解物的修饰产物,并测定它们的ACE抑制活性、IC_(50)值和抗氧化活性。结果表明,酪蛋白水解物的ACE抑制活性随修饰程度的增加而提高,并且都高于未经修饰的酪蛋白水解物,其IC_(50)降低至21.0~25.1μg/mL,表明添加外源氨基酸可提高修饰产物的ACE抑制活性,但添加不同种氨基酸的影响不显著。类蛋白反应修饰后,产物的抗氧化活性明显提高,且远高于酪蛋白水解物。添加不同种外源性氨基酸对抗氧化活性的影响不同:添加苯丙氨酸的修饰产物的DPPH和还原能力最高,添加亮氨酸的修饰产物羟自由基清除活性最高。
Hypertension is a serious risk factor for cardiovascular disease such as heart failure, stroke, coronary heart disease and myocardial infarction. It is especially dangerous because it often has no warning signs or symptoms. It was reported that more than 12000 thousands of peoples died from the cardio- and cerebro-vascular diseases resulted from hypertension every year in the world. Hypertension has now become the first killer to people’s health and is the great public problem. Recently, many researches demonstrated that casein is not only sources of nutrients, but may also be ones of biologieally active peptides, among which ACE-inhibitory peptides have received the most attention for its safe and no side effects nature in the therapy of hypertension. These pepetides show great promise in the development of a novel physiologically functional food for preventing hypertension as well as for therapeutic purposes. In order to prepare bioactivie peptides with high activity from milk proteins, casein hydrolysates were modified by plastein reaction with Alcalase in the presence of extrinsic amino acids in the present work.
The bioactive peptides were prepared by hydrolyzing casein with Alcalase, an alkaline protease from Alcalase 2.4L FG. Casein hydrolysates were prepared by incubating casein with Alcalase for 6 h, and exhibited the highest ACE-inhibitory activity (IC_(50)=42.2μg/mL) with a DH 12.4% and a DPPH radical scavenging activity of 41.8%. The ACE-inhibitory activity of the casein hydrolysates prepapred changed as the DH of casein hydrolysates increased during hydorlysis. When the DH of casein hydrolysates was too low, the hydrolysates only had little ACE-inhibitory activity because the ACE inhibitory peptides were not fully released from the casein. When the DH of casein hydrolysates was too high, the ACE-inhibitory peptides generated were destroyed by protease, which made them lost their ability to inhibit the ACE.
Four reaction conditions including addition level of amino acids, enzyme addition, reaction temperature and the types of amino acids for the Plastein reaction of the casein hydrolysates were optimized by a central composite design and response surface methodology analysis with the decrease of free amino groups in the reaction mixture as the response. When the concentration of casein hydrolysates and reaction time were fixed at 35% (w/w) and 6 h, the practical results indicated that the addition level of amino acids, reaction temperature and the types of amino acid added had significant impacts on the plastein reaction of the casein hydrolysates, while the addition level of Alcalase only had little influence. The effects of these reaction condictions on the Plastein reaction of the casein hydrolysates behaved similar profiles when added amino acid was phenylalanine, leucine or valine, respectively. The optimal conditions were thus selected to be an addition level of amino acid of 0.6 mol/mol free amino groups (hydrolysates), enzyme addition of 3 kU/g proteins and reaction temperature of 40℃. The factors impacted Plastein reaction of the casein hydrolysates significantly was in the order of addition level of amino acids and reaction temperature.
Three modified casein hydrolysates were prepared with the selected suitable conditions in the presence of phenylalanine, leucine and valine, respectively. The analysis results indicated that the ACE-inhibitory or antioxidant activities of the modified casein hydrolysates increased as the extent of modification increased. The IC_(50) values of the modified hydrolysates were in range of 21.0 to 25.1μg/mL, which indicates that the ACE-inhibitory activities of the modified hydrolysates were improved by the Plastein reaction and addition of amino acids. The types of amino acids were not important to the activity of the modified hydrolysates. Antioxidant activity of the modified casein hydrolysates was also significantly improved. The antioxidant activity of the modified casein hydrolysates was different when different extrinsic amino acids were added to the casein hydrolysates. DPPH radical scavenging and reducing activity of the modified casein hydrolysates had the highest value when phenylalanine was added to the casein hydrolysates, while hydroxyl radical scavenging of the modified casein hydrolysates had the highest value when leucine was added to the casein hydrolysates.
利用Alcalase 2.4L FG蛋白酶水解酪蛋白,制备生物活性肽。酪蛋白水解物的ACE抑制活性最高值出现的水解时间为6h,其相应的水解度为12.4%、IC_(50)值为42.2μg/mL、DPPH自由基清除率为41.8%。酪蛋白水解物的ACE抑制活性和水解度之间有一定的关系:当酪蛋白水解物的水解度较低时,酪蛋白中具有ACE抑制活性的片段未被充分释放出来,导致酪蛋白水解物ACE抑制活性低;当酪蛋白水解物的水解度过高时,酪蛋白ACE抑制肽进一步酶解,从而失去它们的ACE抑制性。
利用中心组合设计和响应面分析法,优化类蛋白反应条件。固定酪蛋白水解物的浓度为35%(m/m),反应时间为6 h,以反应体系中游离氨基减少量为响应值,考察氨基酸添加量、酶添加量、反应温度及3种外源性氨基酸对类蛋白反应程度的影响。研究发现:(1)氨基酸添加量、反应温度、氨基酸种类对类蛋白反应的影响显著,而酶添加量对类蛋白反应的影响不大。(2)在分别添加亮氨酸、苯丙氨酸、缬氨酸后,同样研究反应条件对酪蛋白水解物进行类蛋白反应的影响,发现所得到研究结果是相似的。得到在3种外源性氨基酸添加下酪蛋白水解物类蛋白反应的最适反应条件为:氨基酸添加量0.6 mol/mol、酶添加量3 kU/g蛋白、反应温度40℃;(3)对类蛋白反应影响的最主要因素为氨基酸添加量、反应温度。
分别添加苯丙氨酸、亮氨酸、缬氨酸于酪蛋白水解物进行类蛋白反应,制备3个酪蛋白水解物的修饰产物,并测定它们的ACE抑制活性、IC_(50)值和抗氧化活性。结果表明,酪蛋白水解物的ACE抑制活性随修饰程度的增加而提高,并且都高于未经修饰的酪蛋白水解物,其IC_(50)降低至21.0~25.1μg/mL,表明添加外源氨基酸可提高修饰产物的ACE抑制活性,但添加不同种氨基酸的影响不显著。类蛋白反应修饰后,产物的抗氧化活性明显提高,且远高于酪蛋白水解物。添加不同种外源性氨基酸对抗氧化活性的影响不同:添加苯丙氨酸的修饰产物的DPPH和还原能力最高,添加亮氨酸的修饰产物羟自由基清除活性最高。
Hypertension is a serious risk factor for cardiovascular disease such as heart failure, stroke, coronary heart disease and myocardial infarction. It is especially dangerous because it often has no warning signs or symptoms. It was reported that more than 12000 thousands of peoples died from the cardio- and cerebro-vascular diseases resulted from hypertension every year in the world. Hypertension has now become the first killer to people’s health and is the great public problem. Recently, many researches demonstrated that casein is not only sources of nutrients, but may also be ones of biologieally active peptides, among which ACE-inhibitory peptides have received the most attention for its safe and no side effects nature in the therapy of hypertension. These pepetides show great promise in the development of a novel physiologically functional food for preventing hypertension as well as for therapeutic purposes. In order to prepare bioactivie peptides with high activity from milk proteins, casein hydrolysates were modified by plastein reaction with Alcalase in the presence of extrinsic amino acids in the present work.
The bioactive peptides were prepared by hydrolyzing casein with Alcalase, an alkaline protease from Alcalase 2.4L FG. Casein hydrolysates were prepared by incubating casein with Alcalase for 6 h, and exhibited the highest ACE-inhibitory activity (IC_(50)=42.2μg/mL) with a DH 12.4% and a DPPH radical scavenging activity of 41.8%. The ACE-inhibitory activity of the casein hydrolysates prepapred changed as the DH of casein hydrolysates increased during hydorlysis. When the DH of casein hydrolysates was too low, the hydrolysates only had little ACE-inhibitory activity because the ACE inhibitory peptides were not fully released from the casein. When the DH of casein hydrolysates was too high, the ACE-inhibitory peptides generated were destroyed by protease, which made them lost their ability to inhibit the ACE.
Four reaction conditions including addition level of amino acids, enzyme addition, reaction temperature and the types of amino acids for the Plastein reaction of the casein hydrolysates were optimized by a central composite design and response surface methodology analysis with the decrease of free amino groups in the reaction mixture as the response. When the concentration of casein hydrolysates and reaction time were fixed at 35% (w/w) and 6 h, the practical results indicated that the addition level of amino acids, reaction temperature and the types of amino acid added had significant impacts on the plastein reaction of the casein hydrolysates, while the addition level of Alcalase only had little influence. The effects of these reaction condictions on the Plastein reaction of the casein hydrolysates behaved similar profiles when added amino acid was phenylalanine, leucine or valine, respectively. The optimal conditions were thus selected to be an addition level of amino acid of 0.6 mol/mol free amino groups (hydrolysates), enzyme addition of 3 kU/g proteins and reaction temperature of 40℃. The factors impacted Plastein reaction of the casein hydrolysates significantly was in the order of addition level of amino acids and reaction temperature.
Three modified casein hydrolysates were prepared with the selected suitable conditions in the presence of phenylalanine, leucine and valine, respectively. The analysis results indicated that the ACE-inhibitory or antioxidant activities of the modified casein hydrolysates increased as the extent of modification increased. The IC_(50) values of the modified hydrolysates were in range of 21.0 to 25.1μg/mL, which indicates that the ACE-inhibitory activities of the modified hydrolysates were improved by the Plastein reaction and addition of amino acids. The types of amino acids were not important to the activity of the modified hydrolysates. Antioxidant activity of the modified casein hydrolysates was also significantly improved. The antioxidant activity of the modified casein hydrolysates was different when different extrinsic amino acids were added to the casein hydrolysates. DPPH radical scavenging and reducing activity of the modified casein hydrolysates had the highest value when phenylalanine was added to the casein hydrolysates, while hydroxyl radical scavenging of the modified casein hydrolysates had the highest value when leucine was added to the casein hydrolysates.
引文
安广杰,王璋. 2005.类蛋白反应法改性水解明胶的条件.食品发酵工业, 31(3): 83~86.
陈春刚,韩芬霞. 2006.生物活性肽的生理功能及其制备.安徽农业科学, 34(7).
丁海燕. 1999.国内外皮革光亮剂的发展及现状.皮革化工, 16(4): 20~22.
韩飞,于婷婷,周孟良. 2008.酶法生产大豆蛋白ACE抑制肽的研究.食品科学, 29(11): 369~374.
何子安,戚挺华,曾广信,等. 1981.中国蝮蛇(Agkistrodon halys palls)蛇毒中舒缓激肽增强肽的研究.生物化学与生物物理学报, 15(5): 451~458.
李朝慧,罗永康,王全宇. 2005.乳清蛋白酶解制备ACE抑制肽的研究.中国乳品工业, 33(2): 8~11.
李晓晖. 2002.牛乳中酪蛋白的结构特性及其应用.食品工业, 23(1): 29~31.
刘玉德,曹雁平. 2002.生物蛋白肽的开发研究展望.食品科学, 23(8): 319~320.
龙彪,彭志英,陈中,等. 2005.采用木瓜蛋白酶制备乌鸡蛋白肽的研究.食品工业科技, 26(6): 135~138.
荣建华,李小定. 2002.大豆肽体外抗氧化效果的研究.食品科学, 23(11): 118~120.
魏珊,任永忠. 1988.中国江西蝮蛇蛇毒中舒缓激肽增强肽的分离纯化.生物化学与生物物理学报, 20(2): 451~458.
毋瑾超,汪依凡,方长富. 2007.贻贝蛋白酶解降血压肽的降压活性及相对分子质量与氨基酸组成.水产学报, 31(2): 165~170.
吴建平,丁霄霖. 1998.大豆降压肽的研制(I)—生产高活性ACEI肽酶系的筛选.中国油脂, 23(2): 49~51.
吴建平,丁霄霖. 1998b.大豆降压肽的研制III—酶E水解进程参数的研究.中国油脂, 23(4): 12~13,16.
许永红. 1997.蛋白质酶法水解物苦味的控制.食品工业科技, 3: 1~4.
杨萍,邓尚贵,吴玉廉,等. 2002.木瓜蛋白酶在制取青鳞鱼可溶性蛋白中的应用.湛江海洋大学学报, 22(3): 38~41.
张建忠,郦一心. 1998.酪蛋白和酪蛋白制品的开发.中国乳品工业, 26(6): 31~32.
张强,阙国仕,陈红漫. 2005.玉米抗氧化肽的分离制备及其体外抗氧化活性的研究.中国粮油学报, 20(5): 36~39.
周莉,马文雁,刘剑洪等. 1993.酪蛋白接枝聚合改性的研究.深圳大学学报, 10(3-4): 59~65.
Abubakar A, Saito T, Kitazawa H, et al. 1998. Structural Analysis of New Antihypertensive Peptides Derived From Cheese Whey Protein by Proteinase K Digestion. Journal of Dairy Science, 81(12): 3131~3138.
Ali Y, Ahmet M, Ayse A K. 2001. Determination of Antioxidant and Antimicrobial Activities of Rumex Crispus L. Extracts. Journal of Agricultural and Food Chemistry, 49(8): 4083~4089.
Amhar A, Tadao S, Maria, et al. 1996. New Edrivation of the Inhibitory Activity Against
Angiotensin Converting Enzyme (ACE) From Sweet Whey. Yohoku Journal of Agricultural Research, 47:1~2.
Andrews A T, Alichanidis E. 1990. The Plastein Reaction Revisited: Evidence for a Purely Aggregation Reaction Mechanism. Food Chemistry, 35(4): 243~261.
Ashley D V, Temler R, Barclay D, et al. 1983. Amino Acid-Enriched Plasteins: A Source of Limiting Amino Acids for the Weanling Rat. Journal of nutrition, 113(1): 21~27.
Ashok B T, Ali R. 1999. The Aging Paradox: Free Radical Theory of Aging. Experimental Gerontology, 34(3): 293~303.
Berthou J D, Migliore S. 1987. Immunostimulating Properties and Three-Dimensional Structure of Two Tripeptides From Human and Cow Caseins. Fed Eur Biochem Sci, 218(1): 55~58.
Brownsell V L, Williams R J H, Andrews A T. 2001. Application of the Plastein Reaction to Mycoprotein: II. Plastein Properties. Food Chemistry, 72(3): 337~346.
Byun H G, Kim S K. 2002. Structure and Activity of Angiotensin I Converting Enzyme Inhibitory Peptides Derived from Alaskan Pollack Skin. Journal of Biochemistry and Molecular Biology, 35(2): 239~243.
Chabance B, Jolles P, Izquierdo C, et al. 1995. Characterization of an Antithrombotic Peptide FromΚ-Casein in Newborn Plasma After Milk Ingestion. The British Journal of Nutrition, 73: 583~590.
Chen G W, Tsai J S, Sun Pan B. 2007. Purification of Angiotensin I-Converting Enzyme Inhibitory Peptides and Antihypertensive Effect of Milk Produced by Protease-Facilitated Lactic Fermentation. International Dairy Journal, 17(6): 641~647.
Cheung H S, Wang F L, Ondetti M A, et al. 1980. Binding of Peptide Substrates and Inhibitors of the Angiotensin-Converting Enzyme. Journal of Biological Chemistry, 255(25): 401~407.
Cushman D W, Cheung H S, Sabo E F, et al. 1982. Development and Design of Specific Inhibitors of Angiotensin-Converting Enzyme. The American Journal of Cardiology, 49(6): 1390~1394.
Cushman D W, Ondetti M A. 1991. History of the Design of Captopril and Related Inhibitors of Angiotensin Converting Enzyme. Hypertension, 17(4): 589~592.
Daniel H. 2004. Molecular and Integrative Physiology of Intestinal Peptide Transport. Annual Review of Physiology, 66: 361~384.
Dantzig A H, Hoskins J A, Tabas L B, et al. 1994. Association of Intestinal Peptide Transport with a Protein Related to the Cadherin Superfamily Science, 264(5157): 430~433.
Dany D, Sylvie F G, Don E O, et al. Enzyme-Induced Gelation of Extensively Hydrolyzed Whey Proteins by Alcalase: Comparison with the Plastein Reaction and Characterization of Interactions. Journal of Agricultural and Food Chemistry, 51(20): 6036~6042.
David E, Stevenson, Diana J, et al. 1998. Protease-Catalysed Condensation-Oligomerisation of Hydrophobic Peptides as a Means of Flavour Modification. Journal of Molecular Catalysis B: Enzymatic, 5(1-4,15): 39~44.
David E, Stevenson, Diana J, et al. 1998. Protease-Catalyzed Condensation of Peptides as a Potential Means to Reduce the Bitter Taste of Hydrophobic Peptides Found in Protein Hydrolysates. Enzyme and Microbial Technology, 22(2,1): 100~110.
David E, Stevenson, Keith R M, et al. 1999. Use of NMR and Mass Spectrometry to Detect and Quantify Protease-Catalyzed Peptide Bond Formation in Complex Mixtures. Enzyme and Microbial Technology, 25(3-5): 357~369.
Decker E A, Chan W K M, Livisay S A, et al. 1997. Interactions Between Carnosine and the Different Redox States of Myoglobin. Journal of Food Science, 60(6): 1201~1204.
Dong Q Z, Hsieh Y L. 2000. Acrylonitrile Graft Copolymerization of Casein Proteins for Enhanced Solubility and Thermal Properties. Journal of Applied Polymer Science, 77(11): 2543~2551.
Dorer F E, Kahn J R, Lentz K E, et al. 1972. Purification and Properties of Angiotensin- Converting Enzyme from Hog Lung. Circulation Research, 31(3): 356~366.
Doucet D, Gauthier S F, Otter D E, et al. 2003b. Enzyme-Induced Gelation of Extensively Hydrolyzed Whey Proteins by Alcalase: Comparison with the Plastein Reaction and Characterization of Interactions. Journal of Agricultural and Food Chemistry, 51(20): 6036~6042.
Doucet D, Otter D E, Gauthier S F, et al. 2003a. Enzyme-Induced Gelation of Extensively Hydrolyzed Whey Proteins by Alcalase: Peptide Identification and Determination of Enzyme Specificity. Journal of Agricultural and Food Chemistry, 51(21): 6300~6308.
Echeverria V, Ducatenzeiler A, Chen C H, et al. 2005. EndogenousΒ-Amyloid Peptide Synthesis Modulates cAMP Response Element-Regulated Gene Expression in PC12 Cells. Neuroscience, 135(4): 1193~1202.
Erd?s E G, Skidgel R A. 1987. The Angiotensin I-Converting Enzyme. Laboratory Investigation, 56(4): 345~348.
Fei Y J, Kanai Y, Nussberger S, et al. 1994. Expression Cloning of a Mammalian Proton-Coupled Oligopeptide Transporter. Nature, 368: 563~566.
Ferreira I, Pinho O, Mota M V, et al. 2007. Preparation of Ingredients Containing an ACE-Inhibitory Peptide by Tryptic Hydrolysis of Whey Protein Concentrates. International Dairy Journal, 17(5): 481~487.
Ferreira S H, Rocha S M. 1965. Potentiation of Bradykinin and Eledoisin by BPF (Bradykinin Potentiating Factor) from Bothrops Jararaca Venom. Cellular and Molecular Life Sciences, 21(6): 347~349.
Fujimaki M, Kato H, Arai S, et al. 1971. Application of Microbial Proteinases to Soybean and Other Materials to Improve Accept-Ability, Especially Through the Formation of Plastein. Journal of Applied Microbiology, 34(1): 119~131.
Fujita H, Yamafami K, Ohshima K. 2001. Effects of an Ace-Inhibitory Agent, Katsuobushi Oligopeptide, in the Spontaneously Hypertensive Rat and in Borderline and Mildly Hypertensive Subjects. Nutrition Research, 21(8): 1149~1158.
Fumio Y, Kunio S. 1993. Immunological Effects of Dietary Peptide Derived from Soybean Protein. Immunological Effects of Dietary Peptide Derived from Soybean Protein. The Journal of Nutritional Biochemistry, 4(8): 450~457.
Ganapathhy V, Burckhardt G, Leibach F H. 1984. Characteristics of Glycylsarcosine Transport in Rabbit Intestinal Brush-Border Membrane Vesicles. The Journal of Biological Chemistry, 259: 8954~8959.
Gilbert D L. 2000. Fifty Years of Radical Ideas. Annals of the New York Academy of Sciences, 899(1): 1~14.
Gill H S, Doull F, Rutherfurd K J, et al. 2000. Immunoregulatory Peptides in Bovine Milk. The British Journal of Nutrition, 84(1): 111~117.
Goepfert A, Lorenzen P C, Schlimme E. 1999. Peptide Synthesis During in Vitro Proteolysis-Transpeptidation or Condensation? Nahrung, 43(3): 211~212.
Hang G, Yoshiaki K, Masami Y. 2009. Structures and Properties of Antioxidative Peptides Derived from Royal Jelly Protein. Food Chemistry, 113(3): 238~245.
Hans M. 1998. Biochemical Properties of Regulatory Peptides Derived from Mil Proteins. Peptide Science, 43(2): 119~128.
Harman D. 1956. Aging: A Theory Based on Free Radical and Radiation Chemistry. Journal of Gerontology, 11(3): 298~300.
Hata Y, Yamamoto M, Ohni M, et al. 1996. A Placebo-Controlled Study of the Effect of Sour Milk on Blood Pressure in Hypertensive Subjects. American Journal of Clinical Nutrition, 64(5): 767~771.
Hofsten B V, Lalasidis G. 1976. Protease Catalyzed Formation of Plastein Products and Some of Their Properties. Journal of Agricultural and Food Chemistry, 24(3): 460~465.
Jenon Y J, Byun H G, Kim S K. 1999. Improvement of Functional Properties of Cod Frame Protein Hydrolysates Using Ultrafiltration Membranes. Process Biochemistry, 35(5): 471~578.
Johnston C I. 1992. Renin-Angiotensin System: a Dual Tissue and Hormonal System for Cardiovascular Control. Journal of Hypertension, 10(7): S13~S26.
Julio C M, Rolf J. 1979. Papain-Catalyzed Synthesis of Methionine-Enriched Soy Plasteins. Average Chain Length of the Plastein Peptides. Journal of Agricultural and Food Chemistry, 27(6): 1281~1285.
Julius M T, Janusz M, Lisowski J. 1988. A Colostral Protein that Induces the Growth and Differentiation of Resting B Lymphocytes. Journal of Immunology, 140(5): 1366~1371.
Kato H, Suzuki T. 1971. Bradykinin-Potentiating Peptides from the Venom of Agkistrodon Halys. Isolation of Five Bradykinin Potentiators and the Amino Acid Sequences of Two of Them, Potentiators B and C. Biochemistry, 10(6): 972~980.
Kawasaki T, Seki E, Osajima K, et al. 2000. Antihypertensive Effect of Valyl-Tyrosine, a Short Chain Peptide Derived from Sardine Muscle Hydrolyzate, on Mild Hypertensive Subjects. Journal of Human Hypertension, 14(8): 519~523.
Kilara A, Panyam D. 2003. Peptides from Milk Protein and Their Properties. Critical Reviews in Food Science and Nutrition, 43(6): 607~613.
Kim S K, Byun H G, Park P J, et al. 2001. Angiotensin I Converting Enzyme Inhibitory Peptides Purified from Bovine Skin Gelatin Hydrolysate. Journal of Agricultural and Food Chemistry, 49(6): 2992~2997.
Kim S K, Kim Y T, Byun H G, et al. 2001. Isolation and Characterization of Antioxidative Peptides from Gelatin Hydrolysate of Alaska Pollack Skin. Journal of Agricultural and Food Chemistry, 49(4): 1984~1989.
Li Y H, Jiang B, Zhang T, et al. 2008. Antioxidant and Free Radical-Scavenging Activities of Chickpea Protein Hydrolysate (CPH). Food Chemistry, 2008, 106 (2): 444~450.
López-Fandi?o R, Otte J, van Camp J. 2006. Physiological, Chemical and Technological Aspects of Milk-Protein-Derived Peptides with Antihypertensive and ACE-Inhibitory Activity. International Dairy Journal, 16(11): 1277~1293.
Lozano P, Combes D, Iborra J L. 1994. Food Protein Nutrient Improvement by Protease at Reduced Water Activity. Journal of Food Science, 59(4): 876~888.
LV G S, Huo G C, Fu X Y. 2003. Expression of Milk-Derived Antihypetensive Peptide in Escherichia Coli. Journal of Dairy Science, 86(6): 1927~1931.
Maeno M, Yamamoto N, Takano T. 1996. Identification of an Antihypertensive Peptide from Casein Hydrolysate Produced by Proteinase from Lactobacillus Helveticus CP790. Journal of Dairy Science, 79(8): 1316~1321.
Magadi R R, Alan R M.1991. Synthesis of Plastein from Fish Silage. Science of Food and Agriculture, 54(4): 655~658.
Mao X Y, Ni J R, Sun W L, et al. 2007. Value-Added Utilization of Yak Milk Casein for the Production of Angiotensin-I-Converting Enzyme Inhibitory Peptides. Food Chemistry, 103(4): 1282~1287.
Matsufuji H, Matsui T. 1994. Agiotensin I-converting Enzyme Inhibitory Peptides in an Alkaline Protease Hydrolyzate Derived from Sardine Musele. Biosci Biotechnol Biochem, 58(12): 2244~2245.
Matsui T, Li CH, Tanaka T, et al. 2000. Depressor Effect of Wheat Germ Hydrolysate and its Novel Angiotensin I-Converting Enzyme Inhibitory Peptide, Ile-Val-Tyr, and the Metabolism in Rat and Human Plasma. Biol Pharm Bull, 23(4): 427~431.
Meisel H, Fitzgerald R J. 2000. Opioid Peptides Encrypted in Intact Milk Protein Sequences. The British Journal of Nutrition, 84(1): 27~31.
Merrifield R B. 1963. Solid Phase Peptide Synthesis. I. The Synthesis of a Tetrapeptide. Journal of the American Chemical Society, 85(14): 2149~2154.
Miguel M, Contreras M M, Recio I, et al. 2009. ACE-Inhibitory and Antihypertensive Properties of a Bovine Casein Hydrolysate. Food Chemistry, 112(1): 211~214.
Miral D, Pawei J, Mustafa B, et al. 2002. Free Radical Inducted Damage to DNA:
Mechanisms and Measurement. Free Radical Biology and Medicine, 32(11): 1102~1105. Miyoshi S, Ishikawa H, Kaneko T, et al. 1991. Structures and Activity of
Angiotensin-Converting Enzyme Inhibitors in an Alpha-Zein Hydrolysate. Agricultural and Biological Chemistry, 55(5): 1313~1318.
Monti J C, Jost R. 1979. Papain-Catalyzed Synthesis of Methionine-Enriched Soy Plasteins. Average Chain Length of the Plastein Peptides. Journal of Agricultural and Food Chemistry, 27(6): 1281~1285.
Mullally M M, Meisel H, FitzGerald R J. 1997. Angiotensin-I-Converting Enzyme Inhibitory Activities of Gastric and Pancreatic Proteinase Digests of Whey Proteins. International Dairy Journal, 7(5): 299~303.
Murray B A, Walsh D J, FitzGerald R J. 2004. Modification of the Furanacryloyl-L- Phenylalanyl-Glycylglycine Assay for Determination of Angiotensin-I-Converting Enzyme Inhibitory Activity. Journal of Biochemical and Biophysical Methods, 59(2): 127~137.
Naoyuki Y. 1997. Antihypertensive Peptides Derived from Food Proteins. Biopolymers, 43(2): 129~134.
Nielsena M S, Martinussenb T, Flambardc B, et al. 2009. Peptide Profiles and Angiotensin-I-Converting Enzyme Inhibitory Activity of Fermented Milk prodUcts: Effect of Bacterial Strain, Fermentation pH, and Storage Time. International Dairy Journal, 19(3): 155~165.
Nsimba R Y, KikuzakiH, Konishi Y. 2008. Antioxidant Activity of Various Extracts and Fractions of Chenopodium Quinoa and Amaranthus Spp. Seeds. Food Chemistry, 106(2): 760~766.
Nurminen M L, Vapaatalo H, Korpela R, et al. 2001. Long-Term Intake of Milk Peptides Attenuates Development of Hypertension in Spontaneously Hypertensive Rats. Journal of Physiology and Pharmacology, 52(4): 745~754.
Ondetti M A, Williams N J, Sabo E F, et al. 1971. Angiotensin-Converting Enzyme Inhibitors from the Venom of Bothrops Jararaca. Isolation, Elucidation of Structure, and Synthesis. Biochemistry, 10(22): 4033~4039.
Oren Z, Shai Y. 1997. Selective Lysis of Bacteria but not Mammalian Cells by Diastereomers of Melittin: Structure-Function Study. Biochemistry, 36(7): 1826~1835.
Ortiz-Chao P, Gómez-Ruiz J A, Rastall R A, et al. 2009. Production of Novel ACE Inhibitory Peptides fromβ-Lactoglobulin Using Protease N Amano. International Dairy Journal, 19(2): 69~76.
Otte J, Shalaby S M A, Zakora M, et al. 2007a. Fractionation and Identification of ACE-Inhibitory Peptides fromα-Lactalbumin andβ-Casein Produced by Thermolysin-Catalysed Hydrolysis. International Dairy Journal, 17(12): 1460~1472.
Pascard C, Guilhem J, Vincent M, et al. 1991. Configuration and Preferential Solid-State Conformations of Perindoprilat (S-9780). Comparison with the Crystal Structures of other ACE Inhibitors and Conclusions Related to Structure-Activity Relationships. Journal of Medicinal Chemistry, 34 (2): 663~669.
Pellegrini A, Dettling C, Thomas U, et al. 2001. Isolation and Characterization of Four
Bactericidal Domains in the Bovine Beta-Lactoglobulin. Biochim Biophys Acta, 1526(2): 131~140.
Pihlanto-Lepp?l? A, Koskinen P, Piilola K, et al. 2000. Angiotensin I-Converting Enzyme Inhibitory Properties of Whey Protein Digests: Concentration and Characterization of Active Peptides. Journal of Dairy Research, 67(1): 53~64.
Pripp A H, Isaksson T, Stepaniak L, et al. 2004. Quantitative Structure-Activity Relationship Modelling of ACE-Inhibitory Peptides Derived from Milk Proteins. European Food Research and Technology, 219(6): 579~583.
Robert M C, Razaname A, Mutter M, et al. 2004. Identification of Angiotensin-I-Converting Enzyme Inhibitory Peptides Derived from Sodium Caseinate Hydrolysates Produced by Lactobacillus Helveticus NCC 2765. Journal of Agricultural and Food Chemistry, 52(23): 6923~6931.
Sipola M, Finckenberg P, Korpela R, et al. 2002. Effect of Long-Term Intake of Milk Products on Blood Pressure in Hypertensive Rats. The Journal of Dairy Research, 69(1): 103~111.
Suetsuna K, Maekawa K, Chen J, et al. 2004. Separation and Identification of Antioxidative Peptides from Peptic Digest of Fish Scale Collagen. Journal of National Fisheries University, 52(2): 57~62.
Suetsuna K. 1998. Isolation and Characterization of Angiotensin I-Converting Enzyme Inhibitor Dipeptides Derived from Allium Sativum L (garlic). Journal of Nutritional Biochemistry, 9(7): 415~419.
Sukan G, Andrews A T. 1982a. Application of the Plastein Reaction to Caseins and to Skim Milk Powder I. Protein Hydrolysis and Plastein Formation. Journal of Dairy Research, 49: 265~278.
Sukan G, Andrews A T. 1982b. Application of the Plastein Reaction to Caseins and to Skim Milk Power II. Chemical and Physical Properties of the Plasteins and Mechanism of Plastein Formation. Journal of Dairy Research, 49: 279~293.
Synowiecki J, Jagielka R, Shahidi F. 1996. Preparation of Hydrolysates from Bovine red Blood Cells and Their Debittering Following Plastein Reaction. Food Chemistry, 57(3): 435~439.
Takuwa N, Shimada T, Matsumoto H, et al. 1985. Proton-Coupled Transport of Glycylglycine in Rabbit Renal Brush-Border Membrane Vesicles. Biochimica et Biophysica Acta (BBA) -Biomembranes, 814(1): 186~190.
Teschemacher H. 2003. Opioid Receptor Ligands Derived from Food Proteins. Current Pharmaceutical Design, 9(16): 1331~1344.
Vegarud G E, Langsrud T, Svenning C. 2000. Mineral-Binding Milk Proteins and Peptides; Occurrence, Biochemical Andtechnological Characteristics. The British Journal of Nutrition, 84(1): 91~98.
Vermeirssen V, Van C J, Verstraete W. 2004. Bioavailability of Angiotensin I Converting Enzyme Inhibitory Peptides. The British Journal of Nutrition, 92(3): 357~366.
Vincenzini M T, Lantomasi T, Favilli F. 1989. Glutathione Transport Across Intestinal
Brush-Border Membranes: Effects of Ions, pH,Δψ, and Inhibitors. Biochimica et Biophysica Acta(BBA)-Biomembranes, 987(1): 29~37.
Wang J, Hu J, Cui J et al. 2008. Purification and Identification of a ACE Inhibitory Peptide from Oyster Proteins Hydrolysate and the Antihypertensive Effect of Hydrolysate in Spontaneously Hypertensive Rats. Food Chemistry, 111(2): 302~308.
Wang J, Zhao M, Zhao Q, et al. 2007. Antioxidant Properties of Papain Hydrolysates of Wheat Gluten in Different Oxidation Systems. Food Chemistry, 101(4): 1658~1663.
Williams R J H, Brownsell V L, Andrews A T. 2001. Application of the Plastein Reaction to Mycoprotein: I Plastein Synthesis. Food Chemistry, 72(3): 329~335.
Wu J P, Aluko R E, Muir A D. 2008. Purification of Angiotensin I-Converting Enzyme- Inhibitory Peptides from the Enzymatic Hydrolysate of Defatted Canola Meal. Food Chemistry, 111(4): 942~950.
Yamamoto N, Akino A, Takano T. 1994a. Antihypertensive Effects of Different Kinds of Fermented Milk in Spontaneously Hypertensive Rats. Bioscience, Biotechnology, and Biochemistry, 58(4): 776~778.
Yamashita M, Arai S, Kokubo S, et al. 1975. Synthesis and Characterization of a Glutamic Acid Enriched Plastein with Greater Solubility. Journal of Agricultural and Food Chemistry, 23(1): 27~30.
Yamashita M, Arai S, Matsuyama J, et al. 1970. Enzymic Modification of Proteins in Foodstuffs. Part 4. Bitter Dipeptides as Plastein Building Blocks withα-Chymotrypsin. Agricultural and Biological Chemistry, 34: 1492~1497.
Yamashita M, Arai S, Tanimoto S, et al. 1973. Condensation Reaction Occurring During Plastein Formation byα-Chymotrypsin. Agricultural and Biological Chemistry, 37: 953~954.
Yamashita M, Arai S, Tsai S J, et al. 1971. Plastein Reaction as a Method for Enhancing the Sulfur-Containing Amino Acid Level of Soybean Protein. Journal of Agricultural and Food Chemistry, 19(6): 1151~1154.
Yildirim A., Mavi A, Kara A A. 2001. Determination of antioxidant and antimicrobial activities of Rumex crispus L. extracts. Journal of Agricultural and Food Chemistry 49(8): 4083~4089.
Zealk S, Yu R, Park S et al. 2001. His-His-Leu, An angiotensin I Converting Enzyme Inhibitory Peptide Derived from Korean Soybean Paste, Exerts Antihypertensive Activity in Vivo. Agric Food Chem, 49(6): 3004~3009.
Zhao X H, Wu D, Li T J. 2010. Preparation and the Radical Scavenging Activity of Papain Catalyzed Casein Plasteins. Dairy Sci Technol, 90(5): 521~535.
陈春刚,韩芬霞. 2006.生物活性肽的生理功能及其制备.安徽农业科学, 34(7).
丁海燕. 1999.国内外皮革光亮剂的发展及现状.皮革化工, 16(4): 20~22.
韩飞,于婷婷,周孟良. 2008.酶法生产大豆蛋白ACE抑制肽的研究.食品科学, 29(11): 369~374.
何子安,戚挺华,曾广信,等. 1981.中国蝮蛇(Agkistrodon halys palls)蛇毒中舒缓激肽增强肽的研究.生物化学与生物物理学报, 15(5): 451~458.
李朝慧,罗永康,王全宇. 2005.乳清蛋白酶解制备ACE抑制肽的研究.中国乳品工业, 33(2): 8~11.
李晓晖. 2002.牛乳中酪蛋白的结构特性及其应用.食品工业, 23(1): 29~31.
刘玉德,曹雁平. 2002.生物蛋白肽的开发研究展望.食品科学, 23(8): 319~320.
龙彪,彭志英,陈中,等. 2005.采用木瓜蛋白酶制备乌鸡蛋白肽的研究.食品工业科技, 26(6): 135~138.
荣建华,李小定. 2002.大豆肽体外抗氧化效果的研究.食品科学, 23(11): 118~120.
魏珊,任永忠. 1988.中国江西蝮蛇蛇毒中舒缓激肽增强肽的分离纯化.生物化学与生物物理学报, 20(2): 451~458.
毋瑾超,汪依凡,方长富. 2007.贻贝蛋白酶解降血压肽的降压活性及相对分子质量与氨基酸组成.水产学报, 31(2): 165~170.
吴建平,丁霄霖. 1998.大豆降压肽的研制(I)—生产高活性ACEI肽酶系的筛选.中国油脂, 23(2): 49~51.
吴建平,丁霄霖. 1998b.大豆降压肽的研制III—酶E水解进程参数的研究.中国油脂, 23(4): 12~13,16.
许永红. 1997.蛋白质酶法水解物苦味的控制.食品工业科技, 3: 1~4.
杨萍,邓尚贵,吴玉廉,等. 2002.木瓜蛋白酶在制取青鳞鱼可溶性蛋白中的应用.湛江海洋大学学报, 22(3): 38~41.
张建忠,郦一心. 1998.酪蛋白和酪蛋白制品的开发.中国乳品工业, 26(6): 31~32.
张强,阙国仕,陈红漫. 2005.玉米抗氧化肽的分离制备及其体外抗氧化活性的研究.中国粮油学报, 20(5): 36~39.
周莉,马文雁,刘剑洪等. 1993.酪蛋白接枝聚合改性的研究.深圳大学学报, 10(3-4): 59~65.
Abubakar A, Saito T, Kitazawa H, et al. 1998. Structural Analysis of New Antihypertensive Peptides Derived From Cheese Whey Protein by Proteinase K Digestion. Journal of Dairy Science, 81(12): 3131~3138.
Ali Y, Ahmet M, Ayse A K. 2001. Determination of Antioxidant and Antimicrobial Activities of Rumex Crispus L. Extracts. Journal of Agricultural and Food Chemistry, 49(8): 4083~4089.
Amhar A, Tadao S, Maria, et al. 1996. New Edrivation of the Inhibitory Activity Against
Angiotensin Converting Enzyme (ACE) From Sweet Whey. Yohoku Journal of Agricultural Research, 47:1~2.
Andrews A T, Alichanidis E. 1990. The Plastein Reaction Revisited: Evidence for a Purely Aggregation Reaction Mechanism. Food Chemistry, 35(4): 243~261.
Ashley D V, Temler R, Barclay D, et al. 1983. Amino Acid-Enriched Plasteins: A Source of Limiting Amino Acids for the Weanling Rat. Journal of nutrition, 113(1): 21~27.
Ashok B T, Ali R. 1999. The Aging Paradox: Free Radical Theory of Aging. Experimental Gerontology, 34(3): 293~303.
Berthou J D, Migliore S. 1987. Immunostimulating Properties and Three-Dimensional Structure of Two Tripeptides From Human and Cow Caseins. Fed Eur Biochem Sci, 218(1): 55~58.
Brownsell V L, Williams R J H, Andrews A T. 2001. Application of the Plastein Reaction to Mycoprotein: II. Plastein Properties. Food Chemistry, 72(3): 337~346.
Byun H G, Kim S K. 2002. Structure and Activity of Angiotensin I Converting Enzyme Inhibitory Peptides Derived from Alaskan Pollack Skin. Journal of Biochemistry and Molecular Biology, 35(2): 239~243.
Chabance B, Jolles P, Izquierdo C, et al. 1995. Characterization of an Antithrombotic Peptide FromΚ-Casein in Newborn Plasma After Milk Ingestion. The British Journal of Nutrition, 73: 583~590.
Chen G W, Tsai J S, Sun Pan B. 2007. Purification of Angiotensin I-Converting Enzyme Inhibitory Peptides and Antihypertensive Effect of Milk Produced by Protease-Facilitated Lactic Fermentation. International Dairy Journal, 17(6): 641~647.
Cheung H S, Wang F L, Ondetti M A, et al. 1980. Binding of Peptide Substrates and Inhibitors of the Angiotensin-Converting Enzyme. Journal of Biological Chemistry, 255(25): 401~407.
Cushman D W, Cheung H S, Sabo E F, et al. 1982. Development and Design of Specific Inhibitors of Angiotensin-Converting Enzyme. The American Journal of Cardiology, 49(6): 1390~1394.
Cushman D W, Ondetti M A. 1991. History of the Design of Captopril and Related Inhibitors of Angiotensin Converting Enzyme. Hypertension, 17(4): 589~592.
Daniel H. 2004. Molecular and Integrative Physiology of Intestinal Peptide Transport. Annual Review of Physiology, 66: 361~384.
Dantzig A H, Hoskins J A, Tabas L B, et al. 1994. Association of Intestinal Peptide Transport with a Protein Related to the Cadherin Superfamily Science, 264(5157): 430~433.
Dany D, Sylvie F G, Don E O, et al. Enzyme-Induced Gelation of Extensively Hydrolyzed Whey Proteins by Alcalase: Comparison with the Plastein Reaction and Characterization of Interactions. Journal of Agricultural and Food Chemistry, 51(20): 6036~6042.
David E, Stevenson, Diana J, et al. 1998. Protease-Catalysed Condensation-Oligomerisation of Hydrophobic Peptides as a Means of Flavour Modification. Journal of Molecular Catalysis B: Enzymatic, 5(1-4,15): 39~44.
David E, Stevenson, Diana J, et al. 1998. Protease-Catalyzed Condensation of Peptides as a Potential Means to Reduce the Bitter Taste of Hydrophobic Peptides Found in Protein Hydrolysates. Enzyme and Microbial Technology, 22(2,1): 100~110.
David E, Stevenson, Keith R M, et al. 1999. Use of NMR and Mass Spectrometry to Detect and Quantify Protease-Catalyzed Peptide Bond Formation in Complex Mixtures. Enzyme and Microbial Technology, 25(3-5): 357~369.
Decker E A, Chan W K M, Livisay S A, et al. 1997. Interactions Between Carnosine and the Different Redox States of Myoglobin. Journal of Food Science, 60(6): 1201~1204.
Dong Q Z, Hsieh Y L. 2000. Acrylonitrile Graft Copolymerization of Casein Proteins for Enhanced Solubility and Thermal Properties. Journal of Applied Polymer Science, 77(11): 2543~2551.
Dorer F E, Kahn J R, Lentz K E, et al. 1972. Purification and Properties of Angiotensin- Converting Enzyme from Hog Lung. Circulation Research, 31(3): 356~366.
Doucet D, Gauthier S F, Otter D E, et al. 2003b. Enzyme-Induced Gelation of Extensively Hydrolyzed Whey Proteins by Alcalase: Comparison with the Plastein Reaction and Characterization of Interactions. Journal of Agricultural and Food Chemistry, 51(20): 6036~6042.
Doucet D, Otter D E, Gauthier S F, et al. 2003a. Enzyme-Induced Gelation of Extensively Hydrolyzed Whey Proteins by Alcalase: Peptide Identification and Determination of Enzyme Specificity. Journal of Agricultural and Food Chemistry, 51(21): 6300~6308.
Echeverria V, Ducatenzeiler A, Chen C H, et al. 2005. EndogenousΒ-Amyloid Peptide Synthesis Modulates cAMP Response Element-Regulated Gene Expression in PC12 Cells. Neuroscience, 135(4): 1193~1202.
Erd?s E G, Skidgel R A. 1987. The Angiotensin I-Converting Enzyme. Laboratory Investigation, 56(4): 345~348.
Fei Y J, Kanai Y, Nussberger S, et al. 1994. Expression Cloning of a Mammalian Proton-Coupled Oligopeptide Transporter. Nature, 368: 563~566.
Ferreira I, Pinho O, Mota M V, et al. 2007. Preparation of Ingredients Containing an ACE-Inhibitory Peptide by Tryptic Hydrolysis of Whey Protein Concentrates. International Dairy Journal, 17(5): 481~487.
Ferreira S H, Rocha S M. 1965. Potentiation of Bradykinin and Eledoisin by BPF (Bradykinin Potentiating Factor) from Bothrops Jararaca Venom. Cellular and Molecular Life Sciences, 21(6): 347~349.
Fujimaki M, Kato H, Arai S, et al. 1971. Application of Microbial Proteinases to Soybean and Other Materials to Improve Accept-Ability, Especially Through the Formation of Plastein. Journal of Applied Microbiology, 34(1): 119~131.
Fujita H, Yamafami K, Ohshima K. 2001. Effects of an Ace-Inhibitory Agent, Katsuobushi Oligopeptide, in the Spontaneously Hypertensive Rat and in Borderline and Mildly Hypertensive Subjects. Nutrition Research, 21(8): 1149~1158.
Fumio Y, Kunio S. 1993. Immunological Effects of Dietary Peptide Derived from Soybean Protein. Immunological Effects of Dietary Peptide Derived from Soybean Protein. The Journal of Nutritional Biochemistry, 4(8): 450~457.
Ganapathhy V, Burckhardt G, Leibach F H. 1984. Characteristics of Glycylsarcosine Transport in Rabbit Intestinal Brush-Border Membrane Vesicles. The Journal of Biological Chemistry, 259: 8954~8959.
Gilbert D L. 2000. Fifty Years of Radical Ideas. Annals of the New York Academy of Sciences, 899(1): 1~14.
Gill H S, Doull F, Rutherfurd K J, et al. 2000. Immunoregulatory Peptides in Bovine Milk. The British Journal of Nutrition, 84(1): 111~117.
Goepfert A, Lorenzen P C, Schlimme E. 1999. Peptide Synthesis During in Vitro Proteolysis-Transpeptidation or Condensation? Nahrung, 43(3): 211~212.
Hang G, Yoshiaki K, Masami Y. 2009. Structures and Properties of Antioxidative Peptides Derived from Royal Jelly Protein. Food Chemistry, 113(3): 238~245.
Hans M. 1998. Biochemical Properties of Regulatory Peptides Derived from Mil Proteins. Peptide Science, 43(2): 119~128.
Harman D. 1956. Aging: A Theory Based on Free Radical and Radiation Chemistry. Journal of Gerontology, 11(3): 298~300.
Hata Y, Yamamoto M, Ohni M, et al. 1996. A Placebo-Controlled Study of the Effect of Sour Milk on Blood Pressure in Hypertensive Subjects. American Journal of Clinical Nutrition, 64(5): 767~771.
Hofsten B V, Lalasidis G. 1976. Protease Catalyzed Formation of Plastein Products and Some of Their Properties. Journal of Agricultural and Food Chemistry, 24(3): 460~465.
Jenon Y J, Byun H G, Kim S K. 1999. Improvement of Functional Properties of Cod Frame Protein Hydrolysates Using Ultrafiltration Membranes. Process Biochemistry, 35(5): 471~578.
Johnston C I. 1992. Renin-Angiotensin System: a Dual Tissue and Hormonal System for Cardiovascular Control. Journal of Hypertension, 10(7): S13~S26.
Julio C M, Rolf J. 1979. Papain-Catalyzed Synthesis of Methionine-Enriched Soy Plasteins. Average Chain Length of the Plastein Peptides. Journal of Agricultural and Food Chemistry, 27(6): 1281~1285.
Julius M T, Janusz M, Lisowski J. 1988. A Colostral Protein that Induces the Growth and Differentiation of Resting B Lymphocytes. Journal of Immunology, 140(5): 1366~1371.
Kato H, Suzuki T. 1971. Bradykinin-Potentiating Peptides from the Venom of Agkistrodon Halys. Isolation of Five Bradykinin Potentiators and the Amino Acid Sequences of Two of Them, Potentiators B and C. Biochemistry, 10(6): 972~980.
Kawasaki T, Seki E, Osajima K, et al. 2000. Antihypertensive Effect of Valyl-Tyrosine, a Short Chain Peptide Derived from Sardine Muscle Hydrolyzate, on Mild Hypertensive Subjects. Journal of Human Hypertension, 14(8): 519~523.
Kilara A, Panyam D. 2003. Peptides from Milk Protein and Their Properties. Critical Reviews in Food Science and Nutrition, 43(6): 607~613.
Kim S K, Byun H G, Park P J, et al. 2001. Angiotensin I Converting Enzyme Inhibitory Peptides Purified from Bovine Skin Gelatin Hydrolysate. Journal of Agricultural and Food Chemistry, 49(6): 2992~2997.
Kim S K, Kim Y T, Byun H G, et al. 2001. Isolation and Characterization of Antioxidative Peptides from Gelatin Hydrolysate of Alaska Pollack Skin. Journal of Agricultural and Food Chemistry, 49(4): 1984~1989.
Li Y H, Jiang B, Zhang T, et al. 2008. Antioxidant and Free Radical-Scavenging Activities of Chickpea Protein Hydrolysate (CPH). Food Chemistry, 2008, 106 (2): 444~450.
López-Fandi?o R, Otte J, van Camp J. 2006. Physiological, Chemical and Technological Aspects of Milk-Protein-Derived Peptides with Antihypertensive and ACE-Inhibitory Activity. International Dairy Journal, 16(11): 1277~1293.
Lozano P, Combes D, Iborra J L. 1994. Food Protein Nutrient Improvement by Protease at Reduced Water Activity. Journal of Food Science, 59(4): 876~888.
LV G S, Huo G C, Fu X Y. 2003. Expression of Milk-Derived Antihypetensive Peptide in Escherichia Coli. Journal of Dairy Science, 86(6): 1927~1931.
Maeno M, Yamamoto N, Takano T. 1996. Identification of an Antihypertensive Peptide from Casein Hydrolysate Produced by Proteinase from Lactobacillus Helveticus CP790. Journal of Dairy Science, 79(8): 1316~1321.
Magadi R R, Alan R M.1991. Synthesis of Plastein from Fish Silage. Science of Food and Agriculture, 54(4): 655~658.
Mao X Y, Ni J R, Sun W L, et al. 2007. Value-Added Utilization of Yak Milk Casein for the Production of Angiotensin-I-Converting Enzyme Inhibitory Peptides. Food Chemistry, 103(4): 1282~1287.
Matsufuji H, Matsui T. 1994. Agiotensin I-converting Enzyme Inhibitory Peptides in an Alkaline Protease Hydrolyzate Derived from Sardine Musele. Biosci Biotechnol Biochem, 58(12): 2244~2245.
Matsui T, Li CH, Tanaka T, et al. 2000. Depressor Effect of Wheat Germ Hydrolysate and its Novel Angiotensin I-Converting Enzyme Inhibitory Peptide, Ile-Val-Tyr, and the Metabolism in Rat and Human Plasma. Biol Pharm Bull, 23(4): 427~431.
Meisel H, Fitzgerald R J. 2000. Opioid Peptides Encrypted in Intact Milk Protein Sequences. The British Journal of Nutrition, 84(1): 27~31.
Merrifield R B. 1963. Solid Phase Peptide Synthesis. I. The Synthesis of a Tetrapeptide. Journal of the American Chemical Society, 85(14): 2149~2154.
Miguel M, Contreras M M, Recio I, et al. 2009. ACE-Inhibitory and Antihypertensive Properties of a Bovine Casein Hydrolysate. Food Chemistry, 112(1): 211~214.
Miral D, Pawei J, Mustafa B, et al. 2002. Free Radical Inducted Damage to DNA:
Mechanisms and Measurement. Free Radical Biology and Medicine, 32(11): 1102~1105. Miyoshi S, Ishikawa H, Kaneko T, et al. 1991. Structures and Activity of
Angiotensin-Converting Enzyme Inhibitors in an Alpha-Zein Hydrolysate. Agricultural and Biological Chemistry, 55(5): 1313~1318.
Monti J C, Jost R. 1979. Papain-Catalyzed Synthesis of Methionine-Enriched Soy Plasteins. Average Chain Length of the Plastein Peptides. Journal of Agricultural and Food Chemistry, 27(6): 1281~1285.
Mullally M M, Meisel H, FitzGerald R J. 1997. Angiotensin-I-Converting Enzyme Inhibitory Activities of Gastric and Pancreatic Proteinase Digests of Whey Proteins. International Dairy Journal, 7(5): 299~303.
Murray B A, Walsh D J, FitzGerald R J. 2004. Modification of the Furanacryloyl-L- Phenylalanyl-Glycylglycine Assay for Determination of Angiotensin-I-Converting Enzyme Inhibitory Activity. Journal of Biochemical and Biophysical Methods, 59(2): 127~137.
Naoyuki Y. 1997. Antihypertensive Peptides Derived from Food Proteins. Biopolymers, 43(2): 129~134.
Nielsena M S, Martinussenb T, Flambardc B, et al. 2009. Peptide Profiles and Angiotensin-I-Converting Enzyme Inhibitory Activity of Fermented Milk prodUcts: Effect of Bacterial Strain, Fermentation pH, and Storage Time. International Dairy Journal, 19(3): 155~165.
Nsimba R Y, KikuzakiH, Konishi Y. 2008. Antioxidant Activity of Various Extracts and Fractions of Chenopodium Quinoa and Amaranthus Spp. Seeds. Food Chemistry, 106(2): 760~766.
Nurminen M L, Vapaatalo H, Korpela R, et al. 2001. Long-Term Intake of Milk Peptides Attenuates Development of Hypertension in Spontaneously Hypertensive Rats. Journal of Physiology and Pharmacology, 52(4): 745~754.
Ondetti M A, Williams N J, Sabo E F, et al. 1971. Angiotensin-Converting Enzyme Inhibitors from the Venom of Bothrops Jararaca. Isolation, Elucidation of Structure, and Synthesis. Biochemistry, 10(22): 4033~4039.
Oren Z, Shai Y. 1997. Selective Lysis of Bacteria but not Mammalian Cells by Diastereomers of Melittin: Structure-Function Study. Biochemistry, 36(7): 1826~1835.
Ortiz-Chao P, Gómez-Ruiz J A, Rastall R A, et al. 2009. Production of Novel ACE Inhibitory Peptides fromβ-Lactoglobulin Using Protease N Amano. International Dairy Journal, 19(2): 69~76.
Otte J, Shalaby S M A, Zakora M, et al. 2007a. Fractionation and Identification of ACE-Inhibitory Peptides fromα-Lactalbumin andβ-Casein Produced by Thermolysin-Catalysed Hydrolysis. International Dairy Journal, 17(12): 1460~1472.
Pascard C, Guilhem J, Vincent M, et al. 1991. Configuration and Preferential Solid-State Conformations of Perindoprilat (S-9780). Comparison with the Crystal Structures of other ACE Inhibitors and Conclusions Related to Structure-Activity Relationships. Journal of Medicinal Chemistry, 34 (2): 663~669.
Pellegrini A, Dettling C, Thomas U, et al. 2001. Isolation and Characterization of Four
Bactericidal Domains in the Bovine Beta-Lactoglobulin. Biochim Biophys Acta, 1526(2): 131~140.
Pihlanto-Lepp?l? A, Koskinen P, Piilola K, et al. 2000. Angiotensin I-Converting Enzyme Inhibitory Properties of Whey Protein Digests: Concentration and Characterization of Active Peptides. Journal of Dairy Research, 67(1): 53~64.
Pripp A H, Isaksson T, Stepaniak L, et al. 2004. Quantitative Structure-Activity Relationship Modelling of ACE-Inhibitory Peptides Derived from Milk Proteins. European Food Research and Technology, 219(6): 579~583.
Robert M C, Razaname A, Mutter M, et al. 2004. Identification of Angiotensin-I-Converting Enzyme Inhibitory Peptides Derived from Sodium Caseinate Hydrolysates Produced by Lactobacillus Helveticus NCC 2765. Journal of Agricultural and Food Chemistry, 52(23): 6923~6931.
Sipola M, Finckenberg P, Korpela R, et al. 2002. Effect of Long-Term Intake of Milk Products on Blood Pressure in Hypertensive Rats. The Journal of Dairy Research, 69(1): 103~111.
Suetsuna K, Maekawa K, Chen J, et al. 2004. Separation and Identification of Antioxidative Peptides from Peptic Digest of Fish Scale Collagen. Journal of National Fisheries University, 52(2): 57~62.
Suetsuna K. 1998. Isolation and Characterization of Angiotensin I-Converting Enzyme Inhibitor Dipeptides Derived from Allium Sativum L (garlic). Journal of Nutritional Biochemistry, 9(7): 415~419.
Sukan G, Andrews A T. 1982a. Application of the Plastein Reaction to Caseins and to Skim Milk Powder I. Protein Hydrolysis and Plastein Formation. Journal of Dairy Research, 49: 265~278.
Sukan G, Andrews A T. 1982b. Application of the Plastein Reaction to Caseins and to Skim Milk Power II. Chemical and Physical Properties of the Plasteins and Mechanism of Plastein Formation. Journal of Dairy Research, 49: 279~293.
Synowiecki J, Jagielka R, Shahidi F. 1996. Preparation of Hydrolysates from Bovine red Blood Cells and Their Debittering Following Plastein Reaction. Food Chemistry, 57(3): 435~439.
Takuwa N, Shimada T, Matsumoto H, et al. 1985. Proton-Coupled Transport of Glycylglycine in Rabbit Renal Brush-Border Membrane Vesicles. Biochimica et Biophysica Acta (BBA) -Biomembranes, 814(1): 186~190.
Teschemacher H. 2003. Opioid Receptor Ligands Derived from Food Proteins. Current Pharmaceutical Design, 9(16): 1331~1344.
Vegarud G E, Langsrud T, Svenning C. 2000. Mineral-Binding Milk Proteins and Peptides; Occurrence, Biochemical Andtechnological Characteristics. The British Journal of Nutrition, 84(1): 91~98.
Vermeirssen V, Van C J, Verstraete W. 2004. Bioavailability of Angiotensin I Converting Enzyme Inhibitory Peptides. The British Journal of Nutrition, 92(3): 357~366.
Vincenzini M T, Lantomasi T, Favilli F. 1989. Glutathione Transport Across Intestinal
Brush-Border Membranes: Effects of Ions, pH,Δψ, and Inhibitors. Biochimica et Biophysica Acta(BBA)-Biomembranes, 987(1): 29~37.
Wang J, Hu J, Cui J et al. 2008. Purification and Identification of a ACE Inhibitory Peptide from Oyster Proteins Hydrolysate and the Antihypertensive Effect of Hydrolysate in Spontaneously Hypertensive Rats. Food Chemistry, 111(2): 302~308.
Wang J, Zhao M, Zhao Q, et al. 2007. Antioxidant Properties of Papain Hydrolysates of Wheat Gluten in Different Oxidation Systems. Food Chemistry, 101(4): 1658~1663.
Williams R J H, Brownsell V L, Andrews A T. 2001. Application of the Plastein Reaction to Mycoprotein: I Plastein Synthesis. Food Chemistry, 72(3): 329~335.
Wu J P, Aluko R E, Muir A D. 2008. Purification of Angiotensin I-Converting Enzyme- Inhibitory Peptides from the Enzymatic Hydrolysate of Defatted Canola Meal. Food Chemistry, 111(4): 942~950.
Yamamoto N, Akino A, Takano T. 1994a. Antihypertensive Effects of Different Kinds of Fermented Milk in Spontaneously Hypertensive Rats. Bioscience, Biotechnology, and Biochemistry, 58(4): 776~778.
Yamashita M, Arai S, Kokubo S, et al. 1975. Synthesis and Characterization of a Glutamic Acid Enriched Plastein with Greater Solubility. Journal of Agricultural and Food Chemistry, 23(1): 27~30.
Yamashita M, Arai S, Matsuyama J, et al. 1970. Enzymic Modification of Proteins in Foodstuffs. Part 4. Bitter Dipeptides as Plastein Building Blocks withα-Chymotrypsin. Agricultural and Biological Chemistry, 34: 1492~1497.
Yamashita M, Arai S, Tanimoto S, et al. 1973. Condensation Reaction Occurring During Plastein Formation byα-Chymotrypsin. Agricultural and Biological Chemistry, 37: 953~954.
Yamashita M, Arai S, Tsai S J, et al. 1971. Plastein Reaction as a Method for Enhancing the Sulfur-Containing Amino Acid Level of Soybean Protein. Journal of Agricultural and Food Chemistry, 19(6): 1151~1154.
Yildirim A., Mavi A, Kara A A. 2001. Determination of antioxidant and antimicrobial activities of Rumex crispus L. extracts. Journal of Agricultural and Food Chemistry 49(8): 4083~4089.
Zealk S, Yu R, Park S et al. 2001. His-His-Leu, An angiotensin I Converting Enzyme Inhibitory Peptide Derived from Korean Soybean Paste, Exerts Antihypertensive Activity in Vivo. Agric Food Chem, 49(6): 3004~3009.
Zhao X H, Wu D, Li T J. 2010. Preparation and the Radical Scavenging Activity of Papain Catalyzed Casein Plasteins. Dairy Sci Technol, 90(5): 521~535.