Classification: Original article ELECTROSTATICALLY CONSTRAINED α-HELICAL PEPTIDE INHIBITS REPLICATION OF HIV-1 RESISTANT TO ENFUVIRTIDE

2 α-Helical peptides, such as T-20 (enfuvirtide) and C34, derived from the gp41 carboxyl terminal heptad repeat (C-HR) of HIV-1, inhibit membrane fusion of HIV-1 and the target cells. Although T-20 effectively suppresses the replication of multi-drug resistant HIV variants both in vitro and in vivo, prolonged therapy with T-20 induces emergence of T-20 resistant variants. In order to suppress the emergence of such resistant variants, we introduced charged and hydrophilic amino acids, glutamic acid (E) and lysine (K), at the solvent accessible site of C34. In particular, the modified peptide, SC34EK, demonstrates remarkably potent inhibition of membrane fusion by the resistan