New cyclic RGD peptides: synthesis, characterization, and theoretical activity towards ανβ3 integrin

被引：11

作者：

Vilaca, Helena ^{[1
]}

Ferreira, Paula M. T. ^{[1
]}

Micaelo, Nuno M. ^{[1
]}

机构：

[1] Univ Minho, Ctr Chem, P-4710057 Braga, Portugal

来源：

TETRAHEDRON | 2014年 / 70卷 / 35期

关键词：

Cyclic RGD; Bis-azides; Click chemistry; Integrin alpha(nu)beta(3); Docking experiments; DESIGN; POTENT; ALPHA-V-BETA-3; CONFORMATION; ANTAGONISTS; DOCKING; AZIDES;

D O I：

10.1016/j.tet.2014.06.121

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

Two new cyclic RGD peptides were prepared using a click chemistry approach. The linear RGDfV peptide was synthesized by solid-phase peptide synthesis using a 9-fluorenylmetoxicarbonyl (Fmoc) strategy and a 2-chlorotrityl chloride resin. After coupling 5-hexynoic acid the peptide was cleaved from the resin and linked to propargylamine. The bis-alkynyl RGDfV peptide was then reacted with two different bis-azides by treatment with copper iodide and triethylamine. These two cyclic RGD peptides were characterized by NMR and HRMS. In order to evaluate the interaction of these new compounds with integrin alpha(v)beta(3) docking experiments were carried out and the results compared with those obtained with cyclo(RGDf[N-Me]V) (Cilengitide). The two new cyclic RGD peptides showed a higher affinity to the alpha(v)beta(3) integrin when compared with Cilengitide thus representing two new potential integrin alpha(v)beta(3) antagonists. (C) 2014 Elsevier Ltd. All rights reserved.

引用

页码：5420 / 5427

页数：8

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