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Nat Struct Biol. 1999 Oct;6(10):953-60.

Selection of gp41-mediated HIV-1 cell entry inhibitors from biased combinatorial libraries of non-natural binding elements.

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  • 1Department of Molecular and Cellular Biology, Harvard University, 7 Divinity Ave., Cambridge, Massachusetts 02138, USA.


The trimeric, alpha-helical coiled-coil core of the HIV-1 gp41 ectodomain is thought to be part of a transient, receptor-triggered intermediate in the refolding of the envelope glycoprotein into a fusion-active conformation. In an effort to discover small organic inhibitors that block gp41 activation, we have generated a biased combinatorial chemical library of non-natural binding elements targeted to the gp41 core. From this library of 61,275 potential ligands, we have identified elements that, when covalently attached to a peptide derived from the gp41 outer-layer alpha-helix, contribute to the formation of a stable complex with the inner core and to inhibition of gp41-mediated cell fusion.

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  • Picture story. Keeping HIV out. [Nat Struct Biol. 1999]
  • Battling AIDS. [Nat Struct Biol. 1999]
  • Blocking HIV entry. [Nat Struct Biol. 1999]
[PubMed - indexed for MEDLINE]
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