An improved synthesis of a selective αvβ3-integrin antagonist cyclo(-RGDfK-)

被引：43

作者：

Dai, XD

Su, Z

Liu, JO

机构：

[1] MIT, Ctr Canc Res, Dept Biol, Cambridge, MA 02139 USA

[2] MIT, Ctr Canc Res, Dept Chem, Cambridge, MA 02139 USA

来源：

TETRAHEDRON LETTERS | 2000年 / 41卷 / 33期

关键词：

alpha(v)beta(3)-integrin antagonist; cyclic RGD peptide; solid-phase synthesis;

D O I：

10.1016/S0040-4039(00)01060-1

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

The cyclic pentapeptide cyclo(-Arg-Gly-Asp-D-Phe-Lys-) is a highly potent and selective inhibitor for the alpha(v)beta(3) integrin. A related compound, cyclo(-Arg-Gly-Asp-D-Phe-Val-), is a promising anticancer drug candidate; it inhibits angiogenesis and induces apoptosis in vascular cells. We have developed an improved solid-phase synthesis based on Kessler's procedure to afford cyclo(-RGDfK-) peptide in high purity and high yield in a multi-gram scale. This improved synthesis is environmentally friendly and may be generally applicable to other related cyclic peptide syntheses. (C) 2000 Elsevier Science Ltd. All rights reserved.

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页码：6295 / 6298

页数：4

相关论文

共 19 条

[1] Type II' to type I beta-turn swap changes specificity for integrins [J].

Bach, AC ;

Espina, JR ;

Jackson, SA ;

Stouten, PFW ;

Duke, JL ;

Mousa, SA ;

DeGrado, WF .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1996, 118 (01) :293-294

[2] REQUIREMENT OF VASCULAR INTEGRIN ALPHA(V)BETA(3) FOR ANGIOGENESIS [J].

BROOKS, PC ;

CLARK, RAF ;

CHERESH, DA .

SCIENCE, 1994, 264 (5158) :569-571

[3] INTEGRIN ALPHA(V)BETA(3) ANTAGONISTS PROMOTE TUMOR-REGRESSION BY INDUCING APOPTOSIS OF ANGIOGENIC BLOOD-VESSELS [J].

BROOKS, PC ;

MONTGOMERY, AMP ;

ROSENFELD, M ;

REISFELD, RA ;

HU, TH ;

KLIER, G ;

CHERESH, DA .

CELL, 1994, 79 (07) :1157-1164

[4] Synthesis and solution conformation of cyclo[RGDRGD]: A cyclic peptide with selectivity for the alpha V beta 3 receptor [J].

Burgess, K ;

Lim, D ;

Mousa, SA .

JOURNAL OF MEDICINAL CHEMISTRY, 1996, 39 (22) :4520-4526

[5] THE 2,2,4,6,7-PENTAMETHYLDIHYDROBENZOFURAN-5-SULFONYL GROUP (PBF) AS ARGININE SIDE-CHAIN PROTECTANT [J].

CARPINO, LA ;

SHROFF, H ;

TRIOLO, SA ;

MANSOUR, EME ;

WENSCHUH, H ;

ALBERICIO, F .

TETRAHEDRON LETTERS, 1993, 34 (49) :7829-7832

[6]

CHERESH DA, 1994, INTEGRINS MOL BIOL R

[7] N-methylated cyclic RGD peptides as highly active and selective αvβ3 integrin antagonists [J].

Dechantsreiter, MA ;

Planker, E ;

Mathä, B ;

Lohof, E ;

Hölzemann, G ;

Jonczyk, A ;

Goodman, SL ;

Kessler, H .

JOURNAL OF MEDICINAL CHEMISTRY, 1999, 42 (16) :3033-3040

[8]

EPENETOS AA, 1995, CELL ADHESION MOL CA

[9] MINIMIZATION OF TRYPTOPHAN ALKYLATION FOLLOWING 9-FLUORENYLMETHOXYCARBONYL SOLID-PHASE PEPTIDE-SYNTHESIS [J].

FIELDS, CG ;

FIELDS, GB .

TETRAHEDRON LETTERS, 1993, 34 (42) :6661-6664

[10] DEFINITION OF 2 ANGIOGENIC PATHWAYS BY DISTINCT ALPHA(V) INTEGRINS [J].

FRIEDLANDER, M ;

BROOKS, PC ;

SHAFFER, RW ;

KINCAID, CM ;

VARNER, JA ;

CHERESH, DA .

SCIENCE, 1995, 270 (5241) :1500-1502