Oligoproline helices as structurally defined scaffolds for oligomeric G protein-coupled receptor ligands

被引：24

作者：

Bonger, Kimberly M. ^{[1
]}

Kapoerchan, Varsha V. ^{[1
]}

Grotenbreg, Gijsbert M. ^{[1
]}

van Koppen, Chris J. ^{[2
]}

Timmers, C. Marco ^{[3
]}

van der Marel, Gijsbert A. ^{[1
]}

Overkleeft, Herman S. ^{[1
]}

机构：

[1] Leiden Univ, Leiden Inst Chem, Gorlaeus Labs, Dept Bioorgan Synth, NL-2300 RA Leiden, Netherlands

[2] Schering Plough Res Inst, Dept Mol Pharmacol, NL-5340 BH Oss, Netherlands

[3] Schering Plough Res Inst, Dept Med Chem, NL-5340 BH Oss, Netherlands

来源：

ORGANIC & BIOMOLECULAR CHEMISTRY | 2010年 / 8卷 / 08期

关键词：

POLYPROLINE-II STRUCTURE; BIVALENT LIGANDS; CONFORMATION; STABILITY; AGONISTS; LENGTH;

D O I：

10.1039/b923556f

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

Oligoprolines (OPs) are used as rigid backbone scaffolds for the design of oligomeric ligands that target specific G protein-coupled receptors. The OPs were designed to vary in length, the position and number of the ligand-functionalized residues incorporated. For all synthesized compounds a typical PP type II helix was evidenced by circular dichroism indicating that decoration of the helix with large ligands did not affect the helical conformation. Pharmacological evaluation revealed that oligomerization of an agonist with the use of an oligoproline scaffold showed an increase in potency when compared to the monomeric counterparts.

引用

页码：1881 / 1884

页数：4