微波辅助RGD环肽的固相合成
|
摘要
以2-氯代三苯甲基氯树脂为载体,采用Fmoc/t-Bu/Dmab正交保护策略,在微波辅助下合成了环肽c(fKRGD),收率22.5%,纯度94.5%,其结构经MS(ESI), MS(MALDI-TOF)和HPLC确证。
A cyclic RGD peptide c(fKRGD) was synthesized by microwave assisted Fmoc/t-Bu/Dmab orthogonal protection strategy using 2-CTC resin as supporter, with yield of 22.5% and purity of 94.5%. The structure was confirmed by MS(ESI), MS(MALDI-TOF) and HPLC.
A cyclic RGD peptide c(fKRGD) was synthesized by microwave assisted Fmoc/t-Bu/Dmab orthogonal protection strategy using 2-CTC resin as supporter, with yield of 22.5% and purity of 94.5%. The structure was confirmed by MS(ESI), MS(MALDI-TOF) and HPLC.
引文
[1] HECKMANN D, KESSLER H. Design and chemical synthesis of integrin ligands[J].Methods in Enzymology,2007,426:463-503.
[2] 毕建华,崔艳花. RGD模体在肿瘤诊断与靶向治疗方面的研究现状[J].国际病理科学与临床杂志,2012,32(4):312-315.
[3] 安莲效,李慧,顾月清. RGD肽作为药物靶向配体的研究进展[J].中国生化药物杂志,2010,31(1):66-69.
[4] 杨宇,杨大成,肖晴,等. 含RGD序列环肽以及类似物的合成方法研究[J].有机化学,2002,22(4):239-247.
[5] 陈敏东,姜玲,万方,等. 基于固相方法的环肽合成研究进展[J].南京信息工程大学学报(自然科学版),2013,5(3):193-200.
[6] YAMADA K, NAGASHIMA I, HACHISU M, et al. Efficient solid-phase synthesis of cyclic RGD peptides under controlled microwave heating[J].Tetrahedron Letters,2012,53(9):1066-1070.
[7] TALA S R, SCHNELL S M, HASKELL L C. Microwave-assisted solid-phase synthesis of side-chain to side-chain lactam-bridge cyclic peptides[J].Bioorganic & Medicinal Chemistry Letters,2015,25(24):5708-5711.
[8] PALASEK S A, COX Z J, COLLINS J M. Limiting racemization and aspartimide formation in microwave-enhanced Fmoc solid phase peptide synthesis[J].Journal of Peptide Science,2010,13(3):143-148.
[9] 杨明,王卫国,李佩华,等. 微波作用下的多肽固相缩合反应及动力学研究[J].有机化学,2008,28(5):851-856.
[10] 岑涛,周成,武秀明,等. 微波辐射在多肽合成中的研究进展[J].化学世界,2009,50(7):439-442.
[11] 王锡平. RGD环肽合成制备工艺:CN 103588863A[P].2014.
[12] GONCALVES M, ESTIEU G K, LAIN G, et al. On-resin cyclization of a head-to-tail cyclopeptide using an allyldimethylsilyl polys resin[J].Tetrahedron,2005,61(32):7789-7795.
[13] CONROY T, JOLLIFFE K A, PAYNE R J. Efficient use of the Dmab protecting group: applications for the solid-phase synthesis of N-linked glycopeptides[J].Organic & Biomolecular Chemistry,2009,7(11):2255-2258.
[14] CUDIC M, WADE J D, OTVOS J L. Convenient synthesis of a head-to-tail cyclic peptide containing an expanded ring[J].Tetrahedron Letters,2000,41(23):4527-4531.
[15] XU C L, QIN C G, ZHANG R J, et al. Solid-phase synthesis and antibiotic activities of cyclodecapeptides on the scaffold of naturally occurring Laterocidin[J].Bioorganic & Medicinal Chemistry Letters,2010,20(1):164-167.
[16] WENG C C, BARRIE W B, DAVID J E, et al. A novel 4-aminobenzyl ester-based carboxyl- protecting group for synthesis of atypical peptides by Fmoc-tBu solid-phase Chemistry[J].Journal of Chemical Society:Chemical Communication,1995:2209-2210.
[2] 毕建华,崔艳花. RGD模体在肿瘤诊断与靶向治疗方面的研究现状[J].国际病理科学与临床杂志,2012,32(4):312-315.
[3] 安莲效,李慧,顾月清. RGD肽作为药物靶向配体的研究进展[J].中国生化药物杂志,2010,31(1):66-69.
[4] 杨宇,杨大成,肖晴,等. 含RGD序列环肽以及类似物的合成方法研究[J].有机化学,2002,22(4):239-247.
[5] 陈敏东,姜玲,万方,等. 基于固相方法的环肽合成研究进展[J].南京信息工程大学学报(自然科学版),2013,5(3):193-200.
[6] YAMADA K, NAGASHIMA I, HACHISU M, et al. Efficient solid-phase synthesis of cyclic RGD peptides under controlled microwave heating[J].Tetrahedron Letters,2012,53(9):1066-1070.
[7] TALA S R, SCHNELL S M, HASKELL L C. Microwave-assisted solid-phase synthesis of side-chain to side-chain lactam-bridge cyclic peptides[J].Bioorganic & Medicinal Chemistry Letters,2015,25(24):5708-5711.
[8] PALASEK S A, COX Z J, COLLINS J M. Limiting racemization and aspartimide formation in microwave-enhanced Fmoc solid phase peptide synthesis[J].Journal of Peptide Science,2010,13(3):143-148.
[9] 杨明,王卫国,李佩华,等. 微波作用下的多肽固相缩合反应及动力学研究[J].有机化学,2008,28(5):851-856.
[10] 岑涛,周成,武秀明,等. 微波辐射在多肽合成中的研究进展[J].化学世界,2009,50(7):439-442.
[11] 王锡平. RGD环肽合成制备工艺:CN 103588863A[P].2014.
[12] GONCALVES M, ESTIEU G K, LAIN G, et al. On-resin cyclization of a head-to-tail cyclopeptide using an allyldimethylsilyl polys resin[J].Tetrahedron,2005,61(32):7789-7795.
[13] CONROY T, JOLLIFFE K A, PAYNE R J. Efficient use of the Dmab protecting group: applications for the solid-phase synthesis of N-linked glycopeptides[J].Organic & Biomolecular Chemistry,2009,7(11):2255-2258.
[14] CUDIC M, WADE J D, OTVOS J L. Convenient synthesis of a head-to-tail cyclic peptide containing an expanded ring[J].Tetrahedron Letters,2000,41(23):4527-4531.
[15] XU C L, QIN C G, ZHANG R J, et al. Solid-phase synthesis and antibiotic activities of cyclodecapeptides on the scaffold of naturally occurring Laterocidin[J].Bioorganic & Medicinal Chemistry Letters,2010,20(1):164-167.
[16] WENG C C, BARRIE W B, DAVID J E, et al. A novel 4-aminobenzyl ester-based carboxyl- protecting group for synthesis of atypical peptides by Fmoc-tBu solid-phase Chemistry[J].Journal of Chemical Society:Chemical Communication,1995:2209-2210.