Engineering a CD4 mimetic inhibiting the binding of the human immunodeficiency virus-1 (HIV-1) envelope glycoprotein gp120 to human lymphocyte CD4 by the transfer of a CD4 functional site to a small natural scaffold

被引：17

作者：

Drakopoulou, E ^{[1
]}

Vizzavona, J ^{[1
]}

Vita, C ^{[1
]}

机构：

[1] CEA, Dept Ingn & Etud Prot, CE Saclay, F-91190 Gif Sur Yvette, France

来源：

LETTERS IN PEPTIDE SCIENCE | 1998年 / 5卷 / 2-3期

关键词：

active site transfer; chimeric mini-protein; drug lead; HIV inhibitor;

D O I：

10.1023/A:1008837427367

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：

The solvent-exposed CDR2-like region of human CD4 was transferred to the structural scaffold of scorpion charybdotoxin, as a means to reproduce that site in a native-like conformation. The chimeric mini-protein (33 amino acids long), obtained by solid-phase synthesis, is able to specifically prevent the interaction of HIV-1 gp120 with CD4. This CD4 mimetic may represent a valuable tool in the study of the HIV-cell interactions and as a lead in the development of antiviral drugs.

引用

页码：241 / 245

页数：5

共 12 条

[1] 3-DIMENSIONAL STRUCTURE OF NATURAL CHARYBDOTOXIN IN AQUEOUS-SOLUTION BY H-1-NMR - CHARYBDOTOXIN POSSESSES A STRUCTURAL MOTIF FOUND IN OTHER SCORPION TOXINS [J].

BONTEMS, F ;

ROUMESTAND, C ;

BOYOT, P ;

GILQUIN, B ;

DOLJANSKY, Y ;

MENEZ, A ;

TOMA, F .

EUROPEAN JOURNAL OF BIOCHEMISTRY, 1991, 196 (01) :19-28

[2] REFINED STRUCTURE OF CHARYBDOTOXIN - COMMON MOTIFS IN SCORPION TOXINS AND INSECT DEFENSINS [J].

BONTEMS, F ;

ROUMESTAND, C ;

GILQUIN, B ;

MENEZ, A ;

TOMA, F .

SCIENCE, 1991, 254 (5037) :1521-1523

[3]

CAPON DJ, 1991, ANNU REV IMMUNOL, V9, P649, DOI 10.1146/annurev.iy.09.040191.003245

[4] A HOT-SPOT OF BINDING-ENERGY IN A HORMONE-RECEPTOR INTERFACE [J].

CLACKSON, T ;

WELLS, JA .

SCIENCE, 1995, 267 (5196) :383-386

[5] Changing the structural context of a functional beta-hairpin - Synthesis and characterization of a chimera containing the curaremimetic loop of a snake toxin in the scorpion alpha/beta scaffold [J].

Drakopoulou, E ;

ZinnJustin, S ;

Guenneugues, M ;

Gilquin, B ;

Menez, A ;

Vita, C .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (20) :11979-11987

[6] Host factors and the pathogenesis of HIV-induced disease [J].

Fauci, AS .

NATURE, 1996, 384 (6609) :529-534

[7]

KING DS, 1990, INT J PEPT PROT RES, V36, P255

[8]

PIERRET B, 1995, INT J PEPT PROT RES, V46, P471

[9] CD4 - ITS STRUCTURE, ROLE IN IMMUNE FUNCTION AND AIDS PATHOGENESIS, AND POTENTIAL AS A PHARMACOLOGICAL TARGET [J].

SWEET, RW ;

TRUNEH, A ;

HENDRICKSON, WA .

CURRENT OPINION IN BIOTECHNOLOGY, 1991, 2 (04) :622-633

[10] SCORPION TOXINS AS NATURAL SCAFFOLDS FOR PROTEIN ENGINEERING [J].

VITA, C ;

ROUMESTAND, C ;

TOMA, F ;

MENEZ, A .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (14) :6404-6408

← 1 2 →