title: 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.
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.
authors.affiliation: Rega Institute for Medical Research, Katholieke Universiteit Leuven, Leuven, Belgium. Dirk.Daelemans@uz.kuleuven.ac.be
authors.forename: D
authors.initials: D
authors.lastname: Daelemans
authors.forename: D
authors.initials: D
authors.lastname: Schols
authors.forename: M
authors.initials: M
authors.lastname: Witvrouw
authors.forename: C
authors.initials: C
authors.lastname: Pannecouque
authors.forename: S
authors.initials: S
authors.lastname: Hatse
authors.forename: S
authors.initials: S
authors.lastname: van Dooren
authors.forename: F
authors.initials: F
authors.lastname: Hamy
authors.forename: T
authors.initials: T
authors.lastname: Klimkait
authors.forename: E
authors.initials: E
authors.lastname: de Clercq
authors.forename: A M
authors.initials: AM
authors.lastname: VanDamme
mesh_terms: D019380:Anti-HIV Agents / Q000494:pharmacology*; D000911:Antibodies, Monoclonal / Q000276:immunology; D001667:Binding, Competitive; D001692:Biological Transport; D002118:Calcium / Q000378:metabolism; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015967:Gene Expression Regulation, Viral / Q000187:drug effects; D015696:Gene Products, tat / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D015756:Genes, tat / Q000187:drug effects; D054303:HIV Reverse Transcriptase / Q000187:drug effects / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D015498:HIV-2 / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000821:virology; D009842:Oligopeptides / Q000494:pharmacology*; D034444:Peptoids; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors* / Q000276:immunology; D015533:Transcriptional Activation / Q000187:drug effects; D014162:Transfection; D014407:Tumor Cells, Cultured; D019065:Virus Assembly / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects; D054322:tat Gene Products, Human Immunodeficiency Virus
chemical_list: D019380:Anti-HIV Agents; D000911:Antibodies, Monoclonal; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D015696:Gene Products, tat; D009842:Oligopeptides; D034444:Peptoids; D019718:Receptors, CXCR4; D054322:tat Gene Products, Human Immunodeficiency Virus; C402842:CGP 64222; D054303:HIV Reverse Transcriptase; D002118:Calcium