Application of tri- and tetrasubstituted alkene dipeptide mimetics to conformational studies of cyclic RGD peptides
Application of tri- and tetrasubstituted alkene dipeptide mimetics to conformational studies of cyclic RGD peptides
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DOI：
10.1016/j.tet.2005.11.033
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发表时间：
2006-02-13
期刊：
影响因子：
2.1
通讯作者：
Fujii, N
中科院分区：
文献类型：
--
作者：
Oishi, S;Miyamoto, K;Fujii, N
首次将新型psi[(E)-Cx=Cx]型烯烃二肽异构体用于环状生物活性多肽(X=H或Me)的构象研究。为了探索Kessler‘s环状RGD多肽的生物活性构象，利用了环(-精氨酸-甘氨酸-天冬氨酸-D-苯丙氨酸-Val-)1和环(-精氨酸-甘氨酸-天冬氨酸-D-苯丙氨酸-N-MeVal-)2，D-苯丙氨酸[(E)-CX=CX]-L-Val-型二肽异构体，含有二、三和四取代的烯烃，其中含有伽马甲基化的异构体，已被报道为潜在的II型β转角启动子。所有(E)-烯类伪肽3-6对α(V)-β(3)整合素的拮抗活性均高于1，但效价略低于2。核磁共振氢谱的详细结构分析表明，在多肽3-6中没有观察到具有代表性的II‘型β/γ主干排列。相反，基于1H核磁共振数据，多肽3-6的构象被估计为更类似于N-甲基化多肽2的构象。(C)2005爱思唯尔有限公司。保留所有权利。
The first application of a combination of novel psi[(E)-CX=CX]-type alkene dipeptide isosteres to conformation studies of cyclic bioactive peptides was carried out (X= H or Me). For exploration of bioactive conformations of Kessler's cyclic RGD peptides, cyclo(-Arg-Gly-ASP-D-Phe-Val-) 1 and cyclo(-Arg-Gly-ASP-D-Phe-N-MeVal-) 2, D-Phe-psi[(E)-CX=CX]-L-Val-type dipeptide isosteres were utilized having di-, tri- and tetrasubstituted alkenes containing the gamma-methylated isosteres that have been reported to be potential type II' beta-turn promoters. All of the (E)-alkene pseudopeptides 3-6 exhibited higher antagonistic potency against a(v)beta(3) integrin than 1, although potencies were slightly lower than 2. Detailed structural analysis using H-1 NMR spectroscopy revealed that representative type II' beta/gamma backbone arrangements proposed for 1, were not observed in peptides 3-6. Rather on the basis of 1 H NMR data, the conformations of peptides 3-6 were estimated to be more analogous to those of the N-methylated peptide 2. (c) 2005 Elsevier Ltd. All rights reserved.