Inhibition of HIV Tat-TAR interactions by an antisense oligo-2′-O-methylribonucleoside methylphosphonate

被引：19

作者：

Hamma, T

Saleh, A

Huq, I

Rana, TM

Miller, PS

机构：

[1] Johns Hopkins Univ, Dept Biochem & Mol Biol, Baltimore, MD 21205 USA

[2] Univ Massachusetts, Sch Med, Dept Mol Pharmacol & Biochem, Worcester, MA 01605 USA

[3] Fred Hutchinson Canc Res Ctr, Div Basic Sci, Seattle, WA 98109 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2003年 / 13卷 / 11期

关键词：

D O I：

10.1016/S0960-894X(03)00323-8

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

An antisense oligo-2'-O-methylribonucleotide having alternating methylphosphonate/phosphodiester linkages, 1676, whose sequence is complementary to the apical stem-loop of HIV-1 TAR RNA, was prepared to determine its effects on Tat protein-TAR interaction and Tat-mediated gene transactivation in cell culture. This oligomer and its all-phosphodiester analogue, 1707, were shown to: (1) bind to TAR at 37degreesC with K-d's in the low nM concentration range; (2) inhibit Tat-TAR complex formation; and (3) inhibit expression of a chloramphenicol reporter gene under control of the HIV LTR in HeLa HL3T1 cells in culture. (C) 2003 Elsevier Science Ltd. All rights reserved.

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页码：1845 / 1848

页数：4

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