Progress in identifying peptides and small-molecule inhibitors targeted to gp41 of HIV-1.
During the last decade, a great number of activities have been geared in identifying newer targets for inhibiting HIV infection as well as understanding the targets for already identified anti-HIV-1 agents. The success in converting a proof-of-concept peptide T-20 (previously named DP-178), from the C-terminal heptad repeat (CHR) region of the envelope glycoprotein gp41 of HIV-1, to a drug named enfuvirtide was one of the phenomenal successes in HIV-1 drug discovery research that has been made in recent years. There were many reports of modifying peptides from the N-terminal heptad repeat and CHR regions with the objective of improving their activity. A few laboratories also reported the identification of small-molecule inhibitors that apparently bind to the hydrophobic cavity identified in the gp41 core structure and prevent the CHR peptide binding to the N-terminal heptad repeat peptide, thereby prevent the formation of the typical six-helix bundle, which has been thought to be necessary for the fusion between HIV and cell membranes.
Debnath
Asim K
AK
Laboratory of Molecular Modeling & Drug Design, Lindsley F. Kimball Research Institute of The New York Blood Centre, 310 East 67th Street, New York, NY 10021, USA. adebnath@nybloodcenter.org
D000595:Amino Acid Sequence; D000818:Animals; D019380:Anti-HIV Agents / Q000737:chemistry / Q000494:pharmacology*; D016503:Drug Delivery Systems / Q000379:methods / Q000639:trends*; D015700:HIV Envelope Protein gp41 / Q000235:genetics / Q000378:metabolism*; D015658:HIV Infections / Q000188:drug therapy / Q000235:genetics; D015497:HIV-1 / Q000737:chemistry / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D010455:Peptides / Q000008:administration & dosage* / Q000737:chemistry* / Q000235:genetics
D019380:Anti-HIV Agents; D015700:HIV Envelope Protein gp41; D010455:Peptides