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Protein Design of an HIV-1 Entry Inhibitor

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Science  02 Feb 2001:
Vol. 291, Issue 5505, pp. 884-888
DOI: 10.1126/science.1057453

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Abstract

Human immunodeficiency virus type–1 (HIV-1) membrane fusion is promoted by the formation of a trimer-of-hairpins structure that brings the amino- and carboxyl-terminal regions of the gp41 envelope glycoprotein ectodomain into close proximity. Peptides derived from the carboxyl-terminal region (called C-peptides) potently inhibit HIV-1 entry by binding to the gp41 amino-terminal region. To test the converse of this inhibitory strategy, we designed a small protein, denoted 5-Helix, that binds the C-peptide region of gp41. The 5-Helix protein displays potent (nanomolar) inhibitory activity against diverse HIV-1 variants and may serve as the basis for a new class of antiviral agents. The inhibitory activity of 5-Helix also suggests a strategy for generating an HIV-1 neutralizing antibody response that targets the carboxyl-terminal region of the gp41 ectodomain.

  • * To whom correspondence should be addressed. E-mail: kimadmin{at}wi.mit.edu

  • Present address: Merck Research Laboratories, 770 Sumneytown Pike, West Point, PA 19486, USA.

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