Effect of amino acid replacements, additions and deletions on the antiviral activity of a peptide derived from the HIV-1 GP41 sequence

Pept Res. 1995 Nov-Dec;8(6):345-8.

Abstract

We demonstrated that a synthetic peptide (EWDREINNYTSLIHSLIEESQNQQEKNEQEGGC), designated SJ-2176, corresponding to the HIV-1 IIIB gp41 sequence (637-666), inhibited HIV-1 replication, virus-induced cell-cell fusion and cytopathic effects in both CD4+ T and monocytic cell lines. In this study, we show that lengthening the peptide at either the N- or C-terminus enhanced its activity, while shortening the peptide from either end decreased the antiviral activity. Substitution of conserved residues in SJ-2176 by alanines resulted in a decrease or elimination of antiviral activity. Replacement of arginine and lysine in the peptide by glutamines did not diminish antiviral activity and rendered the peptide resistant to trypsin.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alanine
  • Amino Acid Sequence
  • Amino Acids / chemistry*
  • Antiviral Agents / chemistry*
  • Antiviral Agents / pharmacology
  • Binding Sites
  • Conserved Sequence
  • Electrochemistry
  • HIV Envelope Protein gp41 / chemistry*
  • HIV Envelope Protein gp41 / pharmacology*
  • HIV-1 / chemistry*
  • HIV-1 / drug effects
  • Molecular Sequence Data
  • Peptide Fragments / chemistry*
  • Peptide Fragments / pharmacology*
  • Structure-Activity Relationship
  • Trypsin / metabolism
  • Virus Replication / drug effects

Substances

  • Amino Acids
  • Antiviral Agents
  • HIV Envelope Protein gp41
  • Peptide Fragments
  • SJ 2176
  • Trypsin
  • Alanine