Structure-activity relationship for ETB agonism in truncated endothelin-1 analogs
Saeki, T.; Ihara, M.; Fukuroda, T.; Yano, M.
Biochemistry International 28(2): 305-312
1992
ISSN/ISBN: 0158-5231 PMID: 1456952 Document Number: 395288
The essential part of the ET-B-selective agonist N-acetyl-GluAlaValTyrPheAlaHisLeuAspIleIleTrp (N-Ac-4AlaET-1(10-21)) for ET-B agonism was studied by single amino acid replacement. Single L-alanine substitutions at positions 14, 17, 20 and 21 and the corresponding D-amino acid substitutions at positions 14 and 16 21 resulted in remarkable decreases in ET-B binding activity. Furthermore, these analogs elicited endothelium-dependent vasorelaxation in parallel with Et-B binding activity. These data indicate that the amino acid residues of Phe-14, Leu-17, Ile-20 and Trp-21 and the backbone structure at Phe-14 and His-16 apprx Trp-21 in ET-1 are important for ET-B agonism.