d‐Val22 containing human big endothelin‐1 analog, [d‐Val22]Big ET‐1[16–38], inhibits the endothelin converting enzyme

FEBS Letters

Nomizu, Motoyoshi¹  Morita, Akihito²  Horie, Kenji²  Roller, Peter P.¹  Yokogoshi, Hidehiko²  Okitsu, Misako² 

[1] Laboratory of Medicinal Chemistry, Developmental Therapeutics Program, Division of Cancer Treatment, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA;Laboratory of Nutritional Biochemistry, School of Food and Nutritional Sciences, University of Shizuoka, 52-1 Yada, Shizuoka, 422 Japan

关键词: Endothelin-1;    Endothelin converting enzyme;    d-Amino acid;    Big endothelin-1 analog;    Protease inhibitor;    Dopamine;    ET-1;    endothelin-1;    Big ET-1;    big endothelin-1;    ECE;    endothelin converting enzyme;    DA;    dopamine;   

DOI  :  10.1016/0014-5793(94)01012-9

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Endothelin converting enzyme (ECE) is essential for generation of the biological effects of endothelin-1 (ET-1) from a precursor, big endothelin-1 (Big ET-1). We synthesized four analogs of human Big ET-1[16–38], substituted with single d-amino acids at P1, P2, P1′and P2′ positions. ECE activity was determined using an ET-1 specific radioimmunoassay system. None of the d-amino acid containing Big ET-1 analogs were apparently cleaved by ECE, however, one of the synthetic peptides, [d-Val²²]Big ET-1[16–38], strongly inhibited the ECE activity. Furthermore, when this d-Val²² containing peptide was preadministrated to rat striatum, it was found to inhibit the dopamine release induced by Big ET-1. This result suggests that the d-Val²² containing peptide inhibits the ECE activity in vivo. The d-Val²² containing inhibitor offers hope of developing more potent and highly specific ECE inhibitors of therapeutic significance.

【 授权许可】

Unknown