title: Molecular parameters for the anti-human immunodeficiency virus activity of T22 ([Tyr5,12, Lys7]-polyphemusin II).
abstract: T22 ([Tyr5,12, Lys7]-polyphemusin II) was found to exhibit strong anti-human immunodeficiency virus (HIV) activity and exert its effects on a virus-cell fusion process. In the present study, the all-D enantiomer of T22 and its related compounds were synthesized to examine the molecular parameters required for the interaction of T22 with membrane components of cells or viruses in order to exert this anti-HIV activity. The anti-HIV activity of these analogs was investigated in comparison with their membrane permeability with aspect to large unilamellar vesicles (LUVs). The all-D enantiomer of T22 exhibited a 20-fold lower anti-HIV activity compared with T22, whereas they both showed the same membrane permeability. No positive correlation between anti-HIV activity and membrane permeability was observed. These results suggest that the anti-HIV activity of T22 is mediated through the interaction with chiral component(s) of the cell or virus.
authors.affiliation: Faculty of Phamaceutical Sciences, Kyoto University, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Otaka
authors.forename: H
authors.initials: H
authors.lastname: Tamamura
authors.forename: Y
authors.initials: Y
authors.lastname: Terakawa
authors.forename: M
authors.initials: M
authors.lastname: Masuda
authors.forename: T
authors.initials: T
authors.lastname: Koide
authors.forename: T
authors.initials: T
authors.lastname: Murakami
authors.forename: H
authors.initials: H
authors.lastname: Nakashima
authors.forename: K
authors.initials: K
authors.lastname: Matsuzaki
authors.forename: K
authors.initials: K
authors.lastname: Miyajima
authors.forename: T
authors.initials: T
authors.lastname: Ibuka
mesh_terms: D000595:Amino Acid Sequence; D023181:Antimicrobial Cationic Peptides; D000998:Antiviral Agents / Q000737:chemistry* / Q000494:pharmacology; D002463:Cell Membrane Permeability / Q000187:drug effects; D002478:Cells, Cultured; D002942:Circular Dichroism; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D005452:Fluoresceins / Q000737:chemistry; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism
chemical_list: D023181:Antimicrobial Cationic Peptides; D000998:Antiviral Agents; D005452:Fluoresceins; D010455:Peptides; C076963:T22 protein, synthetic; C007740:fluorexon