Effect of amino acid replacements, additions and deletions on the antiviral activity of a peptide derived from the HIV-1 GP41 sequence.
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.
Jiang
S
S
New York Blood Center, New York, USA.
Lin
K
K
D000409:Alanine; D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry*; D000998:Antiviral Agents / Q000737:chemistry* / Q000494:pharmacology; D001665:Binding Sites; D017124:Conserved Sequence; D004563:Electrochemistry; D015700:HIV Envelope Protein gp41 / Q000737:chemistry* / Q000494:pharmacology*; D015497:HIV-1 / Q000737:chemistry* / Q000187:drug effects; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014357:Trypsin / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects
D000596:Amino Acids; D000998:Antiviral Agents; D015700:HIV Envelope Protein gp41; D010446:Peptide Fragments; C103496:SJ 2176; D014357:Trypsin; D000409:Alanine