RNA PSEUDOKNOTS THAT INHIBIT HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 REVERSE-TRANSCRIPTASE

被引：355

作者：

TUERK, C ^{[1
]}

MACDOUGAL, S ^{[1
]}

GOLD, L ^{[1
]}

机构：

[1] UNIV COLORADO, DEPT MOLEC CELLULAR & DEV BIOL, BOULDER, CO 80309 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 1992年 / 89卷 / 15期

关键词：

AIDS; REVERSE TRANSCRIPTASE INHIBITORS; DIRECTED LIGAND EVOLUTION; RNA SECONDARY STRUCTURE;

D O I：

10.1073/pnas.89.15.6988

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

High-affinity ligands of the reverse transcriptase of human immunodeficiency virus type 1 (HIV-1) were isolated by the SELEX procedure (systematic evolution of ligands by exponential enrichment) from RNA populations randomized at 32 positions. Analysis of these ligands revealed a pseudoknot consensus with primary sequence bias at some positions. We demonstrated that at least one of the ligands inhibits cDNA synthesis by HIV reverse transcriptase but fails to inhibit other reverse transcriptases. These experiments highlight the power of SELEX to yield highly specific ligands that reduce the activity of target proteins. Such ligands may provide therapeutic reagents for viral and other diseases.

引用

页码：6988 / 6992

页数：5

共 24 条

[1] HIV-1 REVERSE-TRANSCRIPTASE SPECIFICALLY INTERACTS WITH THE ANTICODON DOMAIN OF ITS COGNATE PRIMER TRANSFER-RNA [J].

BARAT, C ;

LULLIEN, V ;

SCHATZ, O ;

KEITH, G ;

NUGEYRE, MT ;

GRUNINGERLEITCH, F ;

BARRESINOUSSI, F ;

LEGRICE, SFJ ;

DARLIX, JL .

EMBO JOURNAL, 1989, 8 (11) :3279-3285

[2] CRYSTAL-STRUCTURE OF THE RIBONUCLEASE-H DOMAIN OF HIV-1 REVERSE-TRANSCRIPTASE [J].

DAVIES, JF ;

HOSTOMSKA, Z ;

HOSTOMSKY, Z ;

JORDAN, SR ;

MATTHEWS, DA .

SCIENCE, 1991, 252 (5002) :88-95

[3] CHEMOTHERAPEUTIC APPROACHES TO THE TREATMENT OF THE ACQUIRED-IMMUNE-DEFICIENCY-SYNDROME (AIDS) [J].

DECLERCQ, E .

JOURNAL OF MEDICINAL CHEMISTRY, 1986, 29 (09) :1561-1569

[4] THE BACTERIOPHAGE-T4 DEXA-GENE - SEQUENCE AND ANALYSIS OF A GENE CONDITIONALLY REQUIRED FOR DNA-REPLICATION [J].

GAUSS, P ;

GAYLE, M ;

WINTER, RB ;

GOLD, L .

MOLECULAR AND GENERAL GENETICS, 1987, 206 (01) :24-34

[5] DETAILED MODEL OF REVERSE TRANSCRIPTION AND TESTS OF CRUCIAL ASPECTS [J].

GILBOA, E ;

MITRA, SW ;

GOFF, S ;

BALTIMORE, D .

CELL, 1979, 18 (01) :93-100

[6]

GOLDMAN ME, 1990, MOL PHARMACOL, V38, P20

[7]

HERTZ GZ, 1990, COMPUT APPL BIOSCI, V6, P81

[8] SELEXION - SYSTEMATIC EVOLUTION OF LIGANDS BY EXPONENTIAL ENRICHMENT WITH INTEGRATED OPTIMIZATION BY NONLINEAR-ANALYSIS [J].

IRVINE, D ;

TUERK, C ;

GOLD, L .

JOURNAL OF MOLECULAR BIOLOGY, 1991, 222 (03) :739-761

[9] MECHANISM OF HIV REVERSE-TRANSCRIPTASE - ENZYME PRIMER INTERACTION AS REVEALED THROUGH STUDIES OF A DNTP ANALOG, 3'-AZIDO-DTTP [J].

KEDAR, PS ;

ABBOTTS, J ;

KOVACS, T ;

LESIAK, K ;

TORRENCE, P ;

WILSON, SH .

BIOCHEMISTRY, 1990, 29 (15) :3603-3611

[10] REVERSE-TRANSCRIPTASE FROM HUMAN-IMMUNODEFICIENCY-VIRUS - A SINGLE TEMPLATE-PRIMER BINDING-SITE SERVES 2 PHYSICALLY SEPARABLE CATALYTIC FUNCTIONS [J].

KRUG, MS ;

BERGER, SL .

BIOCHEMISTRY, 1991, 30 (44) :10614-10623

← 1 2 3 →