动物毒素多肽物质基础和药理机制
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摘要
传统中医使用的有毒药用动物在临床中的长期实践和成功成为现代药物开发的宝贵经验和资源。它们被用来治疗多种心血管、神经和免疫等相关疾病。有毒药用动物来源的动物多肽毒素成为开发针对人类重大疾病的重要药物候选分子。本文概述了有毒药用动物来源的蛋白多肽药物的结构特征和药理学作用机制,同时着重介绍了我国具有潜在开发和利用价值的动物毒素的研究进展。
The long history and successful practice of utilization of venomous animals in traditional Chinese medicines provide valuable experience and resources for modern drug development. The venomous animal medicines are used to treat many cardiovascular,nerve and immunologic diseases. Peptide toxins from venomous animals have become important targets for the development of drugs for major human diseases. The structural features and pharmacological mechanisms of protein / peptide drugs from animal toxins are reviewed. At the same time,the progress on animal toxins with potential druggability in China is stressed.
The long history and successful practice of utilization of venomous animals in traditional Chinese medicines provide valuable experience and resources for modern drug development. The venomous animal medicines are used to treat many cardiovascular,nerve and immunologic diseases. Peptide toxins from venomous animals have become important targets for the development of drugs for major human diseases. The structural features and pharmacological mechanisms of protein / peptide drugs from animal toxins are reviewed. At the same time,the progress on animal toxins with potential druggability in China is stressed.
引文
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[2]Yan S,Wang X.Recent advances in research on widow spider venoms and toxins[J].Toxins(Basel),2015,7(12):5055-5067.
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[4]Casewell N R,Wüster W,Vonk F J,et al.Complex cocktails:the evolutionary novelty of venoms[J].Trends Ecol Evol,2013,28(4):219-229.
[5]Prashanth J R,Brust A,Jin A H,et al.Cone snail venomics:from novel biology to novel therapeutics[J].Future Med Chem,2014,6(15):1659-1675.
[6]von Reumont B M,Blanke A,Richter S,et al.The first venomous crustacean revealed by transcriptomics and functional morphology:remipede venom glands express a unique toxin cocktail dominated by enzymes and a neurotoxin[J].Mol Biol Evol,2014,31(1):48-58.
[7]Xu X,Lai R.The chemistry and biological activities of peptides from amphibian skin secretions[J].Chem Rev,2015,115(4):1760-1846.
[8]King G F.Venoms as a platform for human drugs:translating toxins into therapeutics[J].Expert Opin Biol Ther,2011,11(11):1469-1484.
[9]Kini R M.Toxins in thrombosis and haemostasis:potential beyond imagination[J].J Thromb Haemost,2011,9(Suppl1):195-208.
[10]Dutertre S,Lewis R J.Toxin insights into nicotinic acetylcholine receptors[J].Biochem Pharmacol,2006,72(6):661-670.
[11]吕秋敏,赖仞,张云.动物毒素与人类疾病:从单一成分到组学研究,从理化性质到疾病机理,从粗毒利用到理性药物设计[J].动物学研究,2010,31(1):2-16.
[12]Reid P F.Alpha-cobratoxin as a possible therapy for multiple sclerosis:a review of the literature leading to its development for this application[J].Crit Rev Immunol,2007,27(4):291-302.
[13]Assumpcao T C,Ribeiro J M,Francischetti I M.Disintegrins from hematophagous sources[J].Toxins(Basel),2012,4(5):296-322.
[14]Arruda Macêdo J K,Fox J W,de Souza Castro M.Disintegrins from snake venoms and their applications in cancer research and therapy[J].Curr Protein Pept Sci,2015,16(6):532-548.
[15]Zhao H,Gan T X,Liu X D,et al.Identification and characterization of novel reptile cathelicidins from elapid snakes[J].Peptides,2008,29(10):1685-1691.
[16]Wang Y,Hong J,Liu X,et al.Snake cathelicidin from Bungarus fasciatus is a potent peptide antibiotics[J].PLo S One,2008,3(9):e3217.
[17]Jin L,Bai X,Luan N,et al.A Designed Tryptophan-and Lysine/Arginine-Rich Antimicrobial Peptide with Therapeutic Potential for Clinical Antibiotic-Resistant Candida albicans Vaginitis[J].J Med Chem,2016,59(5):1791-1799.
[18]Kostiza T,Meier J.Nerve growth factors from snake venoms:chemical properties,mode of action and biological significance[J].Toxicon,1996,34(7):787-806.
[19]Trummal K,Tnismgi K,Paalme V,et al.Molecular diversity of snake venom nerve growth factors[J].Toxicon,2011,58(4):363-368.
[20]Xu T R,Wang W Y,Huang Y H,et al.A nerve growth factor from the venom of Chinese cobra(Naja naja atra)and its effects on male reproductive system in rats[J].Comp Biochem Physiol C Pharmacol Toxicol Endocrinol,1999,124(2):149-156.
[21]Vogel C W,Fritzinger D C,Gorsuch W B,et al.Complement depletion with humanised cobra venom factor:efficacy in preclinical models of vascular diseases[J].Thromb Haemost,2015,113(3):548-552.
[22]Sun Q Y,Chen G,Guo H,et al.Prolonged cardiac xenograft survival in guinea pig-to-rat model by a highly active cobra venom factor[J].Toxicon,2003,42(3):257-262.
[23]Chen Song S,Zhong S,Xiang Y,et al.Complement inhibition enables renal allograft accommodation and longterm engraftment in presensitized nonhuman primates[J].Am J Transplant,2011,11(10):2057-2066.
[24]Zeng L,Sun Q Y,Jin Y,et al.Molecular cloning and characterization of a complement-depleting factor from king cobra,Ophiophagus Hannah[J].Toxicon,2012,60(3):290-301.
[25]Zhang Y,Wisner A,Xiong Y,et al.A novel plasminogen activator from snake venom.Purification,characterization,and molecular cloning[J].J Biol Chem,1995,270(17):10246-1055.
[26]Rebello Horta C C,Chatzaki M,Rezende B A,et al.Cardiovascular-Active Venom Toxins:An Overview[J].Curr Med Chem,2016,23(6):603-622.
[27]Ogawa R,Stachnik J M,Echizen H.Clinical pharmacokinetics of drugs in patients with heart failure:an update(part 2,drugs administered orally)[J].Clin Pharmacokinet,2014,53(12):1083-1114.
[28]KerkelR,Ulvila J,Magga J.Natriuretic peptides in the regulation of cardiovascular physiology and metabolic events[J].J Am Heart Assoc,2015,4(10):e002423.
[29]Sezai A,Shiono M.Natriuretic peptides for perioperative management of cardiac surgery[J].J Cardiol,2016,67(1):15-21.
[30]Lei W,Zhang Y,Yu G,et al.Cloning and sequence analysis of an Ophiophagus hannah c DNA encoding a precursor of two natriuretic peptide domains[J].Toxicon,2011,57(5):811-816.
[31]Wei L,Yang J,He X,et al.Structure and function of a potent lipopolysaccharide-binding antimicrobial and antiinflammatory peptide[J].J Med Chem,2013,56(9):3546-3556.
[32]Zhang Z,Mu L,Tang J,et al.A small peptide with therapeutic potential for inflammatory acne vulgaris[J].PLo S One,2013,8(8):e72923.
[33]Yang H,Wang X,Liu X,et al.Antioxidant peptidomics reveals novel skin antioxidant system[J].Mol Cell Proteomics,2009,8(3):571-583.
[34]Li J,Wu H,Hong J,et al.Odorranalectin is a small peptide lectin with potential for drug delivery and targeting[J].PLo S One,2008,3(6):e2381.
[35]Wu H,Li J,Zhang Q,et al.A novel small Odorranalectinbearing cubosomes:preparation,brain delivery and pharmacodynamic study on amyloid-β25-35-treated rats following intranasal administration[J].Eur J Pharm Biopharm,2012,80(2):368-378.
[36]Mu L,Tang J,Liu H,et al.A potential wound-healingpromoting peptide from salamander skin[J].FASEB J,2014,28(9):3919-3929.
[37]Liu H,Duan Z,Tang J,et al.A short peptide from frog skin accelerates diabetic wound healing[J].FEBS J,2014,281(20):4633-4643
[38]You D,Hong J,Rong M,et al.The first gene-encoded amphibian neurotoxin[J].J Biol Chem,2009,284(33):22079-22086.
[39]Wei L,Dong L,Zhao T,et al.Analgesic and antiinflammatory effects of the amphibian neurotoxin,anntoxin[J].Biochimie,2011,93(6):995-1000.
[40]Lai R,Takeuchi H,Jonczy J,et al.A thrombin inhibitor from the ixodid tick,Amblyomma hebraeum[J].Gene,2004,342(2):243-249.
[41]Liang J G,Zhang J,Lai R,et al.An opioid peptide from synganglia of the tick,Amblyomma testindinarium[J].Peptides,2005,26(4):603-606
[42]Xu X,Yang H,Ma D,et al.Toward an understanding of the molecular mechanism for successful blood feeding by coupling proteomics analysis with pharmacological testing of horsefly salivary glands[J].Mol Cell Proteomics,2008,7(3):582-590.
[43]Ma D,Wang Y,Yang H,et al.Anti-thrombosis repertoire of blood-feeding horsefly salivary glands[J].Mol Cell Proteomics,2009,8(9):2071-2079.
[44]Mariottini G L,Bonello G,Giacco E,et al.Neurotoxic and neuroactive compounds from Cnidaria:five decades of research….and more[J].Cent Nerv Syst Agents Med Chem,2015,15(2):74-80.
[45]Beeton C,Pennington M W,Norton R S.Analogs of the sea anemone potassium channel blocker Sh K for the treatment of autoimmune diseases[J].Inflamm Allergy Drug Targets,2011,10(5):313-321.
[46]Essack M,Bajic V B,Archer J A.Conotoxins that confer therapeutic possibilities[J].Mar Drugs,2012,10(6):1244-1265.
[47]Rashid M H,Mahdavi S,Kuyucak S.Computational studies of marine toxins targeting ion channels[J].Mar Drugs,2013,11(3):848-869.
[48]Harvey A L.Toxins and drug discovery[J].Toxicon,2014,92:193-200.
[49]Carstens B B,Berecki G,Daniel J T,et al.Structure-activity studies of cysteine-richα-conotoxins that inhibit highvoltage-activated calcium channels via GABAB receptor activation reveal a minimal functional motif[J].Angew Chem Int Ed Engl,2016,55(15):4692-4696.
[50]Adams D J,Callaghan B,Berecki G.Analgesic conotoxins:block and G protein-coupled receptor modulation of N-type(Ca(V)2.2)calcium channels[J].Br J Pharmacol,2012,166(2):486-500.
[51]Sang C N,Barnabe K J,Kern S E.Phase IA clinical trial evaluating the tolerability,pharmacokinetics,and analgesic efficacy of an intrathecally administered neurotensin a analogue in central neuropathic pain following spinal cord injury[J].Clin Pharmacol Drug Dev,2016,5(4):250-258.
[52]Alex A B,Saunders G W,Dalpé-Charron A,et al.CGX-1007 prevents excitotoxic cell death via actions at multiple types of NMDA receptors[J].Neurotoxicology,2011,32(4):392-399.
[53]Lewis R J.Discovery and development of theχ-conopeptide class of analgesic peptides[J].Toxicon,2012,59(4):524-528.
[54]Sharpe I A,Gehrmann J,Loughnan M L,et al.Two new classes of conopeptides inhibit the alpha1-adrenoceptor and noradrenaline transporter[J].Nat Neurosci,2001,4(9):902-907.
[55]Janardhan B,Francois N N,More V S,et al.Scorpion toxin polyptides as therapeutic agents:an overview[J].Protein Pept Lett,2016(in press).
[56]Zhao L,Shi X,Zhao J.Chlorotoxin-conjugated nanoparticles for targeted imaging and therapy of glioma[J].Curr Top Med Chem,2015,15(13):1196-1208.
[57]Janzen K M,Steuber T D,Nisly S A.GLP-1 agonists in type1 diabetes mellitus[J].Ann Pharmacother,2016,50(8):656-665.
[58]Su N,Li Y,Xu T,et al.Exenatide in obese or overweight patients without diabetes:A systematic review and metaanalyses of randomized controlled trials[J].Int J Cardiol,2016,219:293-300.
[59]Uccellatore A,Genovese S,Dicembrini I,et al.Comparison review of short-acting and long-acting glucagon-like peptide-1 receptor agonists[J].Diabetes Ther,2015,6(3):239-256.
[60]Kalia J,Milescu M,Salvatierra J,et al.From foe to friend:using animal toxins to investigate ion channel function[J].J Mol Biol,2015,427(1):158-175.
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