DOI: 10.1073/pnas.201392898. Design of potent inhibitors of HIV-1 entry from the gp41 N-peptide region

Design of potent inhibitors of HIV-1 entry from the gp41 N-peptide region

10.1073/pnas.201392898

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

The HIV-1 gp41 envelope glycoprotein promotes fusion of the virus and cell membranes through the formation of a trimer-of-hairpins structure, in which the amino- and carboxyl-terminal regions of the gp41 ectodomain are brought together. Synthetic peptides derived from these two regions (called N and C peptides, respectively) inhibit HIV-1 entry. In contrast to C peptides, which inhibit in the nanomolar range, N peptides are weak inhibitors with IC 50 values in the micromolar range. To test the hypothesis that the weak inhibition of N peptides results from their tendency to aggregate, we have constructed chimeric variants of the N-peptide region of gp41 in which soluble trimeric coiled coils are fused to portions of the gp41 N peptide. These molecules, which present the N peptide in a trimeric coiled-coil conformation, are remarkably more potent inhibitors than the N peptides themselves and likely target the carboxyl-terminal region of the gp41 ectodomain. The best inhibitors described here inhibit HIV-1 entry at nanomolar concentrations.

Bibliography

Eckert, D. M., & Kim, P. S. (2001). Design of potent inhibitors of HIV-1 entry from the gp41 N-peptide region. Proceedings of the National Academy of Sciences, 98(20), 11187â11192.

Authors 2

Debra M. Eckert (first)
Peter S. Kim (additional)

References 31 Referenced 231

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Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 10:34 a.m.)
Deposited	3 years, 4 months ago (April 13, 2022, 6:56 a.m.)
Indexed	40 minutes ago (Aug. 30, 2025, 6:22 a.m.)
Issued	23 years, 11 months ago (Sept. 25, 2001)
Published	23 years, 11 months ago (Sept. 25, 2001)
Published Online	23 years, 11 months ago (Sept. 25, 2001)
Published Print	23 years, 11 months ago (Sept. 25, 2001)

Funders 0

None

BibTeX

@article{Eckert_2001, title={Design of potent inhibitors of HIV-1 entry from the gp41 N-peptide region}, volume={98}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.201392898}, DOI={10.1073/pnas.201392898}, number={20}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Eckert, Debra M. and Kim, Peter S.}, year={2001}, month=sep, pages={11187–11192} }

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