title: Anti-Tat and anti-HIV activities of trimers of n-alkylglycines.
abstract: Transcription of human immunodeficiency virus (HIV-1) is activated by viral Tat protein which regulates HIV-LTR transcription and elongation. In the present report, the evaluation of the anti-Tat activity of a combinatorial library composed of 5120 N-trialkylglycines is reported. The antiviral activity was studied through luciferase-based assays targeting the HIV-1 promoter activation induced by the HIV-1 Tat protein. We identified five peptoids with specific anti-HIV-1 Tat activity; none of these peptoids affected the binding of HIV-1 Tat protein to the viral TAR RNA. Using a recombinant-virus assay in which luciferase activity correlates with the rate of HIV-1 transcription we have detected that one of the five selected peptoids, NC37-37-15C, is a potent inhibitor of HIV-1-LTR transcription in both primary T lymphocytes and transformed cell lines. The inhibitory effect of NC37-37-15C, which is additive with azidothymidine (AZT), correlates with its ability to inhibit CTD phosphorylation and shows a suitable profile for development of novel anti-HIV-1 drugs. Likewise, the structural simplicity of N-alkylglycine oligomers makes these peptidomimetics amenable to structural manipulation, thus facilitating the optimisation of lead molecules for drug-like properties.
authors.affiliation: Departamento de Biología Celular, Fisiología e Inmunología, Universidad de Córdoba, Facultad de Medicina, Avda. de Menéndez Pidal s/n, E-14004 Córdoba, Spain.
authors.forename: Nieves
authors.initials: N
authors.lastname: Márquez
authors.forename: Rocío
authors.initials: R
authors.lastname: Sancho
authors.forename: Antonio
authors.initials: A
authors.lastname: Macho
authors.forename: Alejandra
authors.initials: A
authors.lastname: Moure
authors.forename: Isabel
authors.initials: I
authors.lastname: Masip
authors.forename: Angel
authors.initials: A
authors.lastname: Messeguer
authors.forename: Eduardo
authors.initials: E
authors.lastname: Muñoz
mesh_terms: D019380:Anti-HIV Agents / Q000494:pharmacology*; D001483:Base Sequence; D020650:Combinatorial Chemistry Techniques; D017931:DNA Primers; D024202:Electrophoretic Mobility Shift Assay; D015696:Gene Products, tat / Q000037:antagonists & inhibitors*; D005998:Glycine / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology*; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D019169:Jurkat Cells; D015394:Molecular Structure; D011108:Polymers / Q000737:chemistry / Q000494:pharmacology*; D054322:tat Gene Products, Human Immunodeficiency Virus
chemical_list: D019380:Anti-HIV Agents; D017931:DNA Primers; D015696:Gene Products, tat; D011108:Polymers; D054322:tat Gene Products, Human Immunodeficiency Virus; D005998:Glycine