A novel anti-HIV synthetic peptide, T-22 ([Tyr5,12,Lys7]-polyphemusin II).
Tachyplesin and polyphemusin are antimicrobial peptides recently isolated from the hemocytes of horseshoe crabs (Tachypleus tridentatus and Limulus polyphemus). We synthesized them and their analogs and examined their antiviral activity against human immunodeficiency virus (HIV) type 1 in vitro. The infection of human T cells with the virus was markedly inhibited by some of them at low concentrations. In this structure-activity study, we found that [Tyr5,12, Lys7]-polyphemusin II, which was designated as T22, had extremely high anti-HIV activity. Its 50% inhibitory concentration (EC50) was 0.008 micrograms/ml, while its 50% cytotoxic concentration (CC50) was 54 micrograms/ml and these values were comparable to those of AZT. This result indicates that T22 would be a potential candidate for the therapy of HIV infection.
Masuda
M
M
Faculty of Pharmaceutical Sciences, Kyoto University, Japan.
Nakashima
H
H
Ueda
T
T
Naba
H
H
Ikoma
R
R
Otaka
A
A
Terakawa
Y
Y
Tamamura
H
H
Ibuka
T
T
Murakami
T
T
D000595:Amino Acid Sequence; D023181:Antimicrobial Cationic Peptides; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D004268:DNA-Binding Proteins; D015497:HIV-1 / Q000187:drug effects* / Q000254:growth & development; D006801:Humans; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis* / Q000494:pharmacology; D010456:Peptides, Cyclic; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D023181:Antimicrobial Cationic Peptides; D000998:Antiviral Agents; D004268:DNA-Binding Proteins; D010455:Peptides; D010456:Peptides, Cyclic; C057636:tachyplesin peptide, Tachypleus tridentatus; C076963:T22 protein, synthetic