DISCOVERY OF A DRUG LEAD EMPLOYING A PEPTIDE LIBRARY - INHIBITION OF HIV-1 TAT AND VIRAL REPLICATION BY THE TRIPEPTIDE YPG-NH2

被引：8

作者：

COFFEN, DL

HUANG, TN

RAMER, SE

WEST, RC

CONNELL, EV

SCHUTT, AD

HSU, MC

机构：

[1] Hoffmann-La Roche Inc., Roche Research Center, Nutley

来源：

ANTIVIRAL CHEMISTRY & CHEMOTHERAPY | 1994年 / 5卷 / 02期

关键词：

D O I：

10.1177/095632029400500210

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

A library of the 8000 tripeptides derivable from coded amino acids was prepared in 20 sets of 400 using solid phase synthesis on a benzhydrylamine resin. The peptide mixtures, as C-terminal amides, were screened for inhibition of secreted alkaline phosphatase expression in a cellular (COS) system wherein a transfected SeAP gene construct was under control of the HIV-1 LTR promoter, activated by the product of a cotransfected HIV Tat gene construct. Thus, YPG-NH2 was discovered as an inhibitor of HIV-1 Tat function and then shown to block HIV replication in a CD4+ T-cell line (CEM) with IC50 = 35 mu M

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页码：128 / 129

页数：2

相关论文

共 10 条

[1] THE SIMULTANEOUS MULTIPLE PRODUCTION OF SOLUTION PHASE PEPTIDES - ASSESSMENT OF THE GEYSEN METHOD OF SIMULTANEOUS PEPTIDE-SYNTHESIS [J].

BRAY, AM ;

MAEJI, NJ ;

GEYSEN, HM .

TETRAHEDRON LETTERS, 1990, 31 (40) :5811-5814

[2] THE TRANSACTIVATOR GENE OF THE HUMAN T-CELL LYMPHOTROPIC VIRUS TYPE-III IS REQUIRED FOR REPLICATION [J].

DAYTON, AI ;

SODROSKI, JG ;

ROSEN, CA ;

GOH, WC ;

HASELTINE, WA .

CELL, 1986, 44 (06) :941-947

[3] THE TRANSACTIVATOR GENE OF HTLV-III IS ESSENTIAL FOR VIRUS-REPLICATION [J].

FISHER, AG ;

FEINBERG, MB ;

JOSEPHS, SF ;

HARPER, ME ;

MARSELLE, LM ;

REYES, G ;

GONDA, MA ;

ALDOVINI, A ;

DEBOUK, C ;

GALLO, RC ;

WONGSTAAL, F .

NATURE, 1986, 320 (6060) :367-371

[4] LIGHT-DIRECTED, SPATIALLY ADDRESSABLE PARALLEL CHEMICAL SYNTHESIS [J].

FODOR, SPA ;

READ, JL ;

PIRRUNG, MC ;

STRYER, L ;

LU, AT ;

SOLAS, D .

SCIENCE, 1991, 251 (4995) :767-773

[5] GENERATION AND USE OF SYNTHETIC PEPTIDE COMBINATORIAL LIBRARIES FOR BASIC RESEARCH AND DRUG DISCOVERY [J].

HOUGHTEN, RA ;

PINILLA, C ;

BLONDELLE, SE ;

APPEL, JR ;

DOOLEY, CT ;

CUERVO, JH .

NATURE, 1991, 354 (6348) :84-86

[6] INHIBITION OF HIV REPLICATION IN ACUTE AND CHRONIC INFECTIONS INVITRO BY A TAT ANTAGONIST [J].

HSU, MC ;

SCHUTT, AD ;

HOLLY, M ;

SLICE, LW ;

SHERMAN, MI ;

RICHMAN, DD ;

POTASH, MJ ;

VOLSKY, DJ .

SCIENCE, 1991, 254 (5039) :1799-1802

[7] INHIBITION OF TYPE-1 HUMAN-IMMUNODEFICIENCY-VIRUS REPLICATION BY A TAT ANTAGONIST TO WHICH THE VIRUS REMAINS SENSITIVE AFTER PROLONGED EXPOSURE IN-VITRO [J].

HSU, MC ;

DHINGRA, U ;

EARLEY, JV ;

HOLLY, M ;

KEITH, D ;

NALIN, CM ;

RICHOU, AR ;

SCHUTT, AD ;

TAM, SY ;

POTASH, MJ ;

VOLSKY, DJ ;

RICHMAN, DD .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (14) :6395-6399

[8] DIRECTED MOLECULAR EVOLUTION [J].

JOYCE, GF .

SCIENTIFIC AMERICAN, 1992, 267 (06) :90-97

[9] A NEW TYPE OF SYNTHETIC PEPTIDE LIBRARY FOR IDENTIFYING LIGAND-BINDING ACTIVITY [J].

LAM, KS ;

SALMON, SE ;

HERSH, EM ;

HRUBY, VJ ;

KAZMIERSKI, WM ;

KNAPP, RJ .

NATURE, 1991, 354 (6348) :82-84

[10] IDENTIFICATION OF HIGHEST-AFFINITY LIGANDS BY AFFINITY SELECTION FROM EQUIMOLAR PEPTIDE MIXTURES GENERATED BY ROBOTIC SYNTHESIS [J].

ZUCKERMANN, RN ;

KERR, JM ;

SIANI, MA ;

BANVILLE, SC ;

SANTI, DV .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (10) :4505-4509