Two interaction modes of the gp41-derived peptides with gp41 and their correlation with antimembrane fusion activity

Peptides derived from gp41 effectively block the gp41-mediated cell fusion or HIV infection. A 36-mer (naDP178), 51-mer (C51) and 27-mer peptide (C27) from the membrane proximal region of gp41 have been examined their interac tion modes with the coiled-coil motif of gp41 presented in thioredoxin (Trx -N) or the bacterially expressed ectodomain of gp41 (Ec-gp41ec). All of the se peptides effectively inhibited the gp il-mediated membrane fusion, howev er, they showed distinct interaction modes with Ec-gp41ec or Trx-N. C51 pep tide bound tightly to Trx-N, and it increased the solubility of Ec-gp41ec, naDP178 showed very weak binding affinity to Trx-N, however, it effectively solubilized Ec-gp41ec. In contrast, C27 peptide showed significant binding to Trx-N; however, it did not affect the solubility of Ec-gp41ec. These in teraction modes of C-peptides were assumed to be related to their different inhibitory mechanism against gp41-mediated cell fusion. (C) 1999 Academic Press.