Identification of novel human immunodeficiency virus type 1-inhibitory peptides based on the antimicrobial peptide database.
To identify novel anti-HIV-1 peptides based on the antimicrobial peptide database (APD; http://aps.unmc.edu/AP/main.php), we have screened 30 candidates and found 11 peptides with 50% effective concentrations (EC(50)) of <10 microM and therapeutic indices (TI) of up to 17. Furthermore, among the eight peptides (with identical amino acid compositions but different sequences) generated by shuffling the sequence of an aurein 1.2 analog, two had a TI twice that of the original sequence. Because antiviral peptides in the database have an arginine/lysine (R/K) ratio of >1, increases in the Arg contents of amphibian maximin H5 and dermaseptin S9 peptides and the database-derived GLK-19 peptide improved the TIs. These examples demonstrate that the APD is a rich resource and a useful tool for developing novel HIV-1-inhibitory peptides.
Wang
Guangshun
G
Eppley Cancer Institute, Room ECI 3018, University of Nebraska Medical Center, 986805 Nebraska Medical Center, Omaha, NE 68198-6805, USA. gwang@unmc.edu
Watson
Karen M
KM
Peterkofsky
Alan
A
Buckheit
Robert W
RW
D000595:Amino Acid Sequence; D029845:Amphibian Proteins / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology; D000818:Animals; D019380:Anti-HIV Agents / Q000737:chemistry / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology; D030562:Databases, Protein; D015195:Drug Design; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D013329:Structure-Activity Relationship
D029845:Amphibian Proteins; D019380:Anti-HIV Agents; D023181:Antimicrobial Cationic Peptides