M. Ferrer et al., Selection of gp41-mediated HIV-1 cell entry inhibitors from biased combinatorial libraries of non-natural binding elements, NAT ST BIOL, 6(10), 1999, pp. 953-960
The trimeric, alpha-helical coiled-coil core of the HIV-1 gp41 ectodomain i
s 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 activatio
n, we have generated a biased combinatorial chemical library of non-natural
binding elements targeted to the gp41 core. From this library of 61,275 po
tential 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.