A second target for the peptoid Tat/transactivation response element inhibitor CGP64222: inhibition of human immunodeficiency virus replication by blocking CXC-chemokine receptor 4-mediated virus entry

D Daelemans; D Schols; M Witvrouw; C Pannecouque; S Hatse; S van Dooren; F Hamy; T Klimkait; E de Clercq; A M VanDamme

A second target for the peptoid Tat/transactivation response element inhibitor CGP64222: inhibition of human immunodeficiency virus replication by blocking CXC-chemokine receptor 4-mediated virus entry

Mol Pharmacol. 2000 Jan;57(1):116-24.

Authors

D Daelemans¹, D Schols, M Witvrouw, C Pannecouque, S Hatse, S van Dooren, F Hamy, T Klimkait, E de Clercq, A M VanDamme

Affiliation

¹ Rega Institute for Medical Research, Katholieke Universiteit Leuven, Leuven, Belgium. Dirk.Daelemans@uz.kuleuven.ac.be

PMID: 10617686

Abstract

The peptoid CGP64222 has been previously demonstrated to inhibit the human immunodeficiency virus (HIV) Tat/transactivation response element complex formation. It has previously been shown that CGP64222 selectively inhibits HIV-1 long terminal repeat-driven gene expression and HIV-1(LAV) replication in lymphocytes. Here, we show that CGP64222 inhibits the replication of a wide range of laboratory strains of HIV-1 and HIV-2 in MT-4 cells. However, CGP64222 proved inactive in MT-4 cells against HIV-1 strains that are resistant to the bicyclams. The bicyclams are known to specifically interact with CXC-chemokine receptor 4, the main coreceptor used by T-tropic HIV strains to enter the cells. Mechanism of action studies revealed that CGP64222 can inhibit the HIV replicative cycle, also through a selective interaction with the CXC-chemokine receptor 4 coreceptor.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anti-HIV Agents / pharmacology*
Antibodies, Monoclonal / immunology
Binding, Competitive
Biological Transport
Calcium / metabolism
Chemokine CXCL12
Chemokines, CXC / metabolism
Dose-Response Relationship, Drug
Gene Expression Regulation, Viral / drug effects
Gene Products, tat / antagonists & inhibitors*
Gene Products, tat / genetics
Gene Products, tat / metabolism
Genes, tat / drug effects
HIV Reverse Transcriptase / drug effects
HIV Reverse Transcriptase / metabolism
HIV-1 / drug effects*
HIV-1 / physiology
HIV-2 / drug effects
HIV-2 / physiology
Humans
Leukocytes, Mononuclear / drug effects
Leukocytes, Mononuclear / virology
Oligopeptides / pharmacology*
Peptoids
Receptors, CXCR4 / antagonists & inhibitors*
Receptors, CXCR4 / immunology
Transcriptional Activation / drug effects
Transfection
Tumor Cells, Cultured
Virus Assembly / drug effects
Virus Replication / drug effects
tat Gene Products, Human Immunodeficiency Virus

Substances

Anti-HIV Agents
Antibodies, Monoclonal
CXCL12 protein, human
Chemokine CXCL12
Chemokines, CXC
Gene Products, tat
Oligopeptides
Peptoids
Receptors, CXCR4
tat Gene Products, Human Immunodeficiency Virus
CGP 64222
HIV Reverse Transcriptase
Calcium