title: Anti HIV-1 virucidal activity of polyamide nucleic acid-membrane transducing peptide conjugates targeted to primer binding site of HIV-1 genome.
abstract: We have shown that polyamide nucleic acids (PNAs) targeted to the PBS (PNA(PBS)) and A-loop (PNA(A-loop)) sequences, when transfected into cells, inhibit HIV-1 replication by blocking the initiation of reverse transcription via destabilizing tRNA(3)(Lys) primer from the viral genome. Here we demonstrate that both PNA(PBS) and PNA(A-loop) conjugated with the membrane-transducing peptide (MTD) vectors penetratin and Tat are rapidly taken up by cells and inhibit HIV-1 replication. Moreover, MTD peptide conjugates of PNA(PBS) and PNA(A-loop) displayed potent virucidal activity against HIV-1. Brief exposure of HIV-1 virions to these conjugates rendered them noninfectious. The IC(50) values for virucidal activity were in the range of approximately 50 nM; IC(50) values for inhibition of HIV-1 replication/infection were 0.5 microM-0.7 microM. The virucidal property of these conjugates suggests that a cocktail of anti-HIV-1 PNA-MTD peptide conjugates targeting critical regions of the HIV-1 genome could serve as a prophylactic agent for inactivating HIV-1 virions after exposure to HIV-1.
authors.affiliation: Department of Biochemistry and Molecular Biology, UMDNJ-New Jersey Medical School, 185 South Orange Avenue, Newark, NJ 07103, USA.
authors.forename: Snehlata
authors.initials: S
authors.lastname: Tripathi
authors.forename: Binay
authors.initials: B
authors.lastname: Chaubey
authors.forename: Beverly E
authors.initials: BE
authors.lastname: Barton
authors.forename: Virendra N
authors.initials: VN
authors.lastname: Pandey
mesh_terms: D019380:Anti-HIV Agents / Q000737:chemistry / Q000494:pharmacology*; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism; D057846:Cell-Penetrating Peptides; D017931:DNA Primers / Q000235:genetics*; D015696:Gene Products, tat / Q000737:chemistry* / Q000378:metabolism; D016679:Genome, Viral / Q000235:genetics*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics*; D020128:Inhibitory Concentration 50; D009696:Nucleic Acids / Q000737:chemistry / Q000494:pharmacology; D009757:Nylons / Q000737:chemistry / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects; D054322:tat Gene Products, Human Immunodeficiency Virus
chemical_list: D019380:Anti-HIV Agents; D002352:Carrier Proteins; D057846:Cell-Penetrating Peptides; D017931:DNA Primers; D015696:Gene Products, tat; D009696:Nucleic Acids; D009757:Nylons; D054322:tat Gene Products, Human Immunodeficiency Virus; C414409:penetratin