Dermorphin and deltorphin heptapeptide analogues: Replacement of Phe residue by Dmp greatly improves opioid receptor affinity and selectivity

被引：16

作者：

Ambo, A ^{[1
]}

Murase, H ^{[1
]}

Niizuma, H ^{[1
]}

Ouchi, H ^{[1
]}

Yamamoto, Y ^{[1
]}

Sasaki, Y ^{[1
]}

机构：

[1] Tohoku Pharmaceut Univ, Aoba Ku, Sendai, Miyagi 9818558, Japan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2002年 / 12卷 / 06期

关键词：

D O I：

10.1016/S0960-894X(02)00035-5

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The usefulness of 2,6-dimethylphenyltalanine (Dmp) as a Phe surrogate in two opioid peptides, dermorphin (DM) and deltorphin 11 (DT), was investigated. Compared to DM, [L-Dmp(3)]DM (1) showed a 170-fold increase in delta affinity and only a 4-fold increase in delta affinity, resulting in a 40-fold improvement in mu receptor selectivity. Compared to DT, [L-Dmp3]DT (3) showed a 22-fold increase in 8 affinity and somewhat of a loss in mu affinity, and consequently a marked (75-fold) improvement in 6 receptor selectivity. The D-Dmp replacement, however, resulted in a great loss in receptor selectivity in each of the peptides. The specific receptor interactions of 1 and 3 were confirmed by in vitro bioassays. Analogues 1 and 3 seem to be useful as pharmacological tools for the study of opioid systems. (C) 2002 Elsevier Science Ltd. All rights reserved.

引用

页码：879 / 881

页数：3

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