Synthesis of protegrin-related peptides and their antibacterial and anti-human immunodeficiency virus activity.
All disulfide analogs (types I, II and III) of protegrin (PG)-1, an 18-residue antimicrobial peptide having two intramolecular disulfide bonds, were synthesized using regioselective disulfide bond formation. Random air-oxidation of the fully reduced PG-1 formed the type III PG-1. In addition, a type III analog containing an amidated carboxy-terminal residue was also prepared. Each analog showed significant and different antibacterial and anti-human immunodeficiency virus (HIV) activity. Deletion of two disulfide bridges caused a significant decrease in activity.
Tamamura
H
H
Faculty of Pharmaceutical Sciences, Kyoto University, Japan.
Murakami
T
T
Horiuchi
S
S
Sugihara
K
K
Otaka
A
A
Takada
W
W
Ibuka
T
T
Waki
M
M
Yamamoto
N
N
Fujii
N
N
D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects; D004220:Disulfides / Q000138:chemical synthesis / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects; D006678:HIV / Q000187:drug effects*; D006801:Humans; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis* / Q000494:pharmacology*; D011506:Proteins / Q000138:chemical synthesis* / Q000494:pharmacology*; D012475:Salmonella / Q000187:drug effects; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D000998:Antiviral Agents; D004220:Disulfides; D010455:Peptides; D011506:Proteins; C094880:protegrin-1