[ALA1,3,11,15]ENDOTHELIN-1 ANALOGS WITH ETB AGONISTIC ACTIVITY

被引：175

作者：

SAEKI, T ^{[1
]}

IHARA, M ^{[1
]}

FUKURODA, T ^{[1
]}

YAMAGIWA, M ^{[1
]}

YANO, M ^{[1
]}

机构：

[1] BANYU PHARMACEUT CO LTD,CENT RES LABS,TOKYO 153,JAPAN

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 1991年 / 179卷 / 01期

关键词：

D O I：

10.1016/0006-291X(91)91367-L

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

A linear peptide analog of endothelin (ET)-1, [Ala1,3,11,15]ET-1 (4AlaET-1), and its truncated peptide analogs were synthesized to study the structural requirements of ET-1 for the recognition of ETs-nonselective ETB receptors. ET-1 exhibited sub-nanomolar binding to two distinct ET receptor subtypes (ETA and ETB), but 4AlaET-1 bound to ETB with an affinity 1,700 times higher than that seen during binding to ETA. The truncated linear peptides 4AlaET-1(6-21), 4AlaET-1(8-21) and N-acetyl-4AlaET-1(10-21) still had high affinity for ETB, whereas 4AlaET-1(6-20) and 4AlaET-1(11-21) displayed remarkably reduced affinity for ETB. Therefore, ET-1 requires the Glu10-Trp21 sequence for ETB binding, but not the disulfide bridges. These ETB-binding peptides elicit endothelium-dependent vasorelaxation of porcine pulmonary arteries in parallel with the binding affinity for ETB, suggesting that they are ETB agonists. © 1991.

引用

页码：286 / 292

页数：7

共 21 条

[1] CLONING AND EXPRESSION OF A CDNA-ENCODING AN ENDOTHELIN RECEPTOR [J].