DOI: 10.1073/pnas.94.25.13426. Inhibition of HIV type 1 infectivity by constrained α-helical peptides: Implications for the viral fusion mechanism

Inhibition of HIV type 1 infectivity by constrained α-helical peptides: Implications for the viral fusion mechanism

10.1073/pnas.94.25.13426

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

Linear peptides derived from the membrane proximal region of the gp41 ectodomain are effective inhibitors of HIV type 1 (HIV-1)-mediated fusion events. These inhibitory peptides lack structure in solution, rendering mechanistic interpretation of their activity difficult. Using structurally constrained analogs of these molecules, we demonstrate that the peptides inhibit infectivity by adopting a helical conformation. Moreover, we show that a specific face of the helix must be exposed to block viral infectivity. Recent crystal structures show that the region of gp41 corresponding to the inhibitory peptides is helical and uses the analogous face to pack against a groove formed by an N-terminal coiled-coil trimer. Our results provide a direct link between the inhibition of HIV-1 infectivity by these peptides and the x-ray structures, and suggest that the conformation of gp41 observed by crystallography represents the fusogenic state. Other agents that block HIV-1 infectivity by binding to this groove may hold promise for the treatment of AIDS.

Bibliography

Judice, J. K., Tom, J. Y. K., Huang, W., Wrin, T., Vennari, J., Petropoulos, C. J., & McDowell, R. S. (1997). Inhibition of HIV type 1 infectivity by constrained Î±-helical peptides: Implications for the viral fusionâmechanism. Proceedings of the National Academy of Sciences, 94(25), 13426â13430.

Authors 7

J. Kevin Judice (first)
Jeffrey Y. K. Tom (additional)
Wei Huang (additional)
Terri Wrin (additional)
Joann Vennari (additional)
Christos J. Petropoulos (additional)
Robert S. McDowell (additional)

References 22 Referenced 119

Dates

Type	When
Created	23 years ago (July 26, 2002, 10:42 a.m.)
Deposited	3 years, 4 months ago (April 13, 2022, 2:56 p.m.)
Indexed	1 year ago (Aug. 12, 2024, 9:11 a.m.)
Issued	27 years, 8 months ago (Dec. 9, 1997)
Published	27 years, 8 months ago (Dec. 9, 1997)
Published Online	27 years, 8 months ago (Dec. 9, 1997)
Published Print	27 years, 8 months ago (Dec. 9, 1997)

Funders 0

None

BibTeX

@article{Judice_1997, title={Inhibition of HIV type 1 infectivity by constrained α-helical peptides: Implications for the viral fusion mechanism}, volume={94}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.94.25.13426}, DOI={10.1073/pnas.94.25.13426}, number={25}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Judice, J. Kevin and Tom, Jeffrey Y. K. and Huang, Wei and Wrin, Terri and Vennari, Joann and Petropoulos, Christos J. and McDowell, Robert S.}, year={1997}, month=dec, pages={13426–13430} }

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