探索缓激肽受体：利用新型肽中羟脯氨酸的醚类绘制几何拓扑结构

Probing the bradykinin receptor: mapping the geometric topography using ethers of hydroxyproline in novel peptides.

作者信息

Kyle D J, Martin J A, Burch R M, Carter J P, Lu S, Meeker S, Prosser J C, Sullivan J P, Togo J, Noronha-Blob L

机构信息

Nova Pharmaceutical Corporation, Baltimore, Maryland 21224.

出版信息

Agents Actions Suppl. 1992;38 ( Pt 1):513-25. doi: 10.1007/978-3-0348-7321-5_63.

DOI:10.1007/978-3-0348-7321-5_63

PMID:1334629

Abstract

Five decapeptides were prepared, each having the generic primary sequence D-Arg0-Arg1-Pro2-Hyp3-Gly4-Thi5-Ser6-X7 -Y8-Arg9. A C-terminal beta-turn was anticipated when X was an alkyl ether of D-4-hydroxyproline in either the cis or trans geometric state and Y was either a Tic or Oic residue. Whereas cis ethers have only very weak receptor affinities, the trans ethers are significantly more potent in binding to guinea pig smooth muscle having Ki values as low as 0.16 nM. Notably, these peptides do not contain a D-aromatic amino acid at position 7 of the primary sequence.

摘要

制备了五种十肽，每种都具有通用的一级序列D-Arg0-Arg1-Pro2-Hyp3-Gly4-Thi5-Ser6-X7 -Y8-Arg9。当X为顺式或反式几何状态的D-4-羟基脯氨酸的烷基醚且Y为Tic或Oic残基时，预期会有一个C端β-转角。虽然顺式醚只有非常弱的受体亲和力，但反式醚与豚鼠平滑肌结合的效力明显更强，其Ki值低至0.16 nM。值得注意的是，这些肽在一级序列的第7位不包含D-芳香族氨基酸。