抗HIV肽T22的构效关系

Structure-activity relationships of an anti-HIV peptide, T22.

作者信息

Tamamura H, Murakami T, Masuda M, Otaka A, Takada W, Ibuka T, Nakashima H, Waki M, Matsumoto A, Yamamoto N

机构信息

Faculty of Pharmaceutical Sciences, Kyoto University, Japan.

出版信息

Biochem Biophys Res Commun. 1994 Dec 30;205(3):1729-35. doi: 10.1006/bbrc.1994.2868.

DOI:10.1006/bbrc.1994.2868

PMID:7811258

Abstract

T22 ([Tyr5,12,Lys7]-polyphemusin II) has been shown to have a strong anti-human immunodeficiency virus (HIV) activity comparable to that of 3'-azido-2',3'-dideoxythymidine (AZT). We studied the structure-anti-HIV activity relationships of T22 and determined the following information. The number of Arg residues in the N-terminal and C-terminal regions of T22 is closely related with anti-HIV activity. Disulfide rings, especially the major disulfide ring, are indispensable for anti-HIV activity and maintenance of the secondary structure. Between two repeats of Tyr-Arg-Lys, which are a characteristic structure contained in T22, Tyr-Arg-Lys in the N-terminal portion is more closely related with anti-HIV activity. We found some compounds having a higher selectivity index (50% cytotoxic concentration/50% effective concentration) than that of T22.

摘要

T22（[酪氨酸5,12，赖氨酸7] - 海胆精蛋白II）已被证明具有强大的抗人类免疫缺陷病毒（HIV）活性，与3'-叠氮-2'，3'-双脱氧胸苷（AZT）相当。我们研究了T22的结构与抗HIV活性之间的关系，并确定了以下信息。T22 N端和C端区域中精氨酸（Arg）残基的数量与抗HIV活性密切相关。二硫键环，尤其是主要的二硫键环，对于抗HIV活性和二级结构的维持是必不可少的。在T22特有的两个酪氨酸-精氨酸-赖氨酸重复序列之间，N端部分的酪氨酸-精氨酸-赖氨酸与抗HIV活性的关系更为密切。我们发现了一些化合物，其选择性指数（50%细胞毒性浓度/50%有效浓度）高于T22。