强效长效生长激素释放因子类似物

Potent long-acting growth hormone releasing factor analogues.

作者信息

Rivier J, Rivier C, Galyean R, Yammamoto G, Vale W

机构信息

Clayton Foundation Laboratories for Peptide Biology, Salk Institute, San Diego, California.

出版信息

Ann N Y Acad Sci. 1988;527:44-50. doi: 10.1111/j.1749-6632.1988.tb26971.x.

DOI:10.1111/j.1749-6632.1988.tb26971.x

PMID:3133968

Abstract

Amidated fragments 1 to 29 of human growth hormone releasing factor, (GRF1-29NH2), were designed to encompass modifications that could prevent degradation by exopeptidases. The NH2-terminus was blocked by either N-methylation of Tyr1 or by introduction of NMeDAla2 while the COOH-terminus was blocked by an N-ethylamide. Other substitutions such as Nle in position 27 for methionine conferred stability toward air oxidation while Asn28, an amino acid substitution found in rat GRF, seemed to confer stronger binding affinity to the GRF receptor. Potency in vitro and duration of action in vivo of [NMeTyr1,Nle27,Asn28]hGRF1-29NHEt (4SG-29) were compared to those of hGRF1-40OH. 4SG-29 was found to be both ten times more potent than hGRF1-40)OH and exhibit significantly extended duration of action.

摘要

人生长激素释放因子（GRF1-29NH2）的酰胺化片段1至29，其设计目的是包含能够防止被外肽酶降解的修饰。NH2端通过Tyr1的N-甲基化或引入NMeDAla2进行封闭，而COOH端通过N-乙基酰胺进行封闭。其他取代，如第27位的Nle取代甲硫氨酸，赋予了对空气氧化的稳定性，而第28位的Asn（在大鼠GRF中发现的一种氨基酸取代）似乎赋予了与GRF受体更强的结合亲和力。将[NMeTyr1,Nle27,Asn28]hGRF1-29NHEt（4SG-29）的体外效力和体内作用持续时间与hGRF1-40OH进行了比较。结果发现，4SG-29的效力比hGRF1-40OH高十倍，并且作用持续时间显著延长。