Structure-activity relationships of an anti-HIV peptide, T22.
T22 ([Tyr5,12,Lys7]-polyphemusin II) has been shown to have a strong anti-human immunodeficiency virus (HIV) activity comparable to that of 3'-azido-2',3'-dideoxythymidine (AZT). We studied the structure-anti-HIV activity relationships of T22 and determined the following information. The number of Arg residues in the N-terminal and C-terminal regions of T22 is closely related with anti-HIV activity. Disulfide rings, especially the major disulfide ring, are indispensable for anti-HIV activity and maintenance of the secondary structure. Between two repeats of Tyr-Arg-Lys, which are a characteristic structure contained in T22, Tyr-Arg-Lys in the N-terminal portion is more closely related with anti-HIV activity. We found some compounds having a higher selectivity index (50% cytotoxic concentration/50% effective concentration) than that of T22.
Tamamura
H
H
Faculty of Pharmaceutical Sciences, Kyoto University, Japan.
Murakami
T
T
Masuda
M
M
Otaka
A
A
Takada
W
W
Ibuka
T
T
Nakashima
H
H
Waki
M
M
Matsumoto
A
A
Yamamoto
N
N
D000595:Amino Acid Sequence; D023181:Antimicrobial Cationic Peptides; D000998:Antiviral Agents / Q000737:chemistry* / Q000494:pharmacology*; D001120:Arginine / Q000737:chemistry; D001665:Binding Sites; D002460:Cell Line; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D004220:Disulfides / Q000737:chemistry; D015497:HIV-1 / Q000187:drug effects* / Q000472:pathogenicity; D006801:Humans; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D023181:Antimicrobial Cationic Peptides; D000998:Antiviral Agents; D004220:Disulfides; D010455:Peptides; C076963:T22 protein, synthetic; D001120:Arginine