含有羰基桥的环脑啡肽和皮啡肽类似物。

Cyclic enkephalin and dermorphin analogues containing a carbonyl bridge.

作者信息

Filip Katarzyna, Oleszczuk Marta, Wójcik Jacek, Chung Nga N, Schiller Peter W, Pawlak Danuta, Zieleniak Agnieszka, Parcińska Agnieszka, Witkowska Ewa, Izdebski Jan

机构信息

Peptide Laboratory, Department of Chemistry, Warsaw University, Pasteura 1, Warsaw, 02-093 Poland.

出版信息

J Pept Sci. 2005 Jun;11(6):347-52. doi: 10.1002/psc.613.

DOI:10.1002/psc.613

PMID:15635652

Abstract

Four cyclic enkephalin analogues and four cyclic dermorphin analogues have been synthesized. Cyclization of linear peptides containing basic amino acid residues of various side chain length in position 2 and 5 (enkephalin analogues) or 2 and 4 (dermorphin analogues) was achieved by treatment with bis-(4-nitrophenyl) carbonate to form a urea unit. The peptides were tested in the guinea-pig ileum (GPI) and mouse vas deferens (MVD) assays. Diverse activity was observed, depending on the size of the ring and the location of the urea unit. The conformation of two dermorphin analogues has been studied: one of high activity (IC(50) = 4.15 nM in the GPI assay) and a second of low activity (IC(50) = 6700 nM in the GPI assay). The conformational space of these peptides was examined using the EDMC method. Using data from the NMR spectra, each peptide was described as an ensemble of conformers. Biological activity was discussed in light of the structural data.

摘要

已合成了四种环脑啡肽类似物和四种环皮啡肽类似物。通过用双（4 - 硝基苯基）碳酸酯处理，使在第2位和第5位（脑啡肽类似物）或第2位和第4位（皮啡肽类似物）含有不同侧链长度碱性氨基酸残基的线性肽环化，形成脲单元。这些肽在豚鼠回肠（GPI）和小鼠输精管（MVD）试验中进行了测试。根据环的大小和脲单元的位置观察到了不同的活性。研究了两种皮啡肽类似物的构象：一种具有高活性（在GPI试验中IC(50) = 4.15 nM），另一种具有低活性（在GPI试验中IC(50) = 6700 nM）。使用EDMC方法研究了这些肽的构象空间。利用核磁共振谱数据，将每种肽描述为构象异构体的集合。根据结构数据讨论了生物活性。