The micelle-associated 3D structures of Boc-Y(SO3)-Nle-G-W-Nle-D-2-phenylethylester (JMV-180) and CCK-8(s) share conformational elements of a calculated CCK1 receptor-bound model

被引：4

作者：

Kumar, Mohanraja ^{[1
,2
]}

Reeve, Joseph R., Jr. ^{[1
,2
]}

Hu, Weidong ^{[3
]}

Miller, Laurence J. ^{[4
]}

Keire, David A. ^{[1
,2
]}

机构：

[1] VA Greater Los Angeles Healthcare Syst, Digest Dis Res Ctr, CURE, Los Angeles, CA 90073 USA

[2] Univ Calif Los Angeles, Sch Med, Div Digest Dis, Los Angeles, CA 90095 USA

[3] Beckman Res Inst, City Hope, Duarte, CA 90010 USA

[4] Mayo Clin, Dept Mol Pharmacol & Expt Therapeut, Scottsdale, AZ 85259 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2008年 / 51卷 / 13期

关键词：

D O I：

10.1021/jm701401j

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

JMV-180 (1) and CCK-8(s) are high affinity ligands at the CCK1 receptor that have similar and different actions via this receptor. Here we calculate the tertiary structure of 1 or CCK-8(s) in the presence of dodecylphosphocholine micelles at pH 5.0 and 35 degrees C from 2D H-1 NMR data recorded at 600 MHz. The NMR derived 3D structures of 1 and CCK-8(s) share a common type I beta-turn around residues Nle3/M3 and G4 and diverge from each other structurally at the N- and C-termini. The fluorescence and circular dichroism spectral properties of these peptides are consistent with their NMR derived structures. The structures determined in the presence of DPC micelles are compared to available models of 1 or CCK-8(s) bound to the CCK1 receptor. For CCK and 1, these comparisons show that DPC micelle associated structures duplicate some important aspects of the models calculated from cross-linking derived constraints at the CCK1 receptor.

引用

页码：3742 / 3754

页数：13