Structure-activity relationship study: short antimicrobial peptides.
Many short antimicrobial peptides (< 18mer) have been identified for the development of therapeutic agents. However, Structure-activity relationship (SAR) studies about short antimicrobial peptides have not been extensively performed. To investigate the relationship between activity and structural parameters such as an alpha-helical structure, a net positive charge and a hydrophobicity, we synthesized and characterized diastereomers, scramble peptides and substituted peptides of the short antimicrobial peptide identified by combinatorial libraries. Circular dichroism (CD) spectra and in vitro activity indicated that an alpha-helical structure correlated with the antimicrobial activity and a beta-sheet structure also satisfied a structural requirement for antimicrobial activity. Most peptides consisting of L-amino acids lost antifungal activity in the presence of heat-inactivated serum, while active diastereomers and a scramble peptide with the beta-sheet structure retained antifungal activity in the same condition.
Oh
J E
JE
Protein Chemistry Laboratory, Mogam Biotechnology Research Institute, Yongin-city, Kyunggi-Do, Korea.
Hong
S Y
SY
Lee
K H
KH
D000900:Anti-Bacterial Agents / Q000737:chemistry*; D000890:Anti-Infective Agents / Q000737:chemistry / Q000494:pharmacology; D000935:Antifungal Agents / Q000737:chemistry / Q000494:pharmacology; D002176:Candida albicans / Q000187:drug effects; D002942:Circular Dichroism; D047630:Depsipeptides; D008968:Molecular Conformation; D009842:Oligopeptides / Q000737:chemistry* / Q000494:pharmacology; D019151:Peptide Library; D017433:Protein Structure, Secondary; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D000935:Antifungal Agents; D047630:Depsipeptides; D009842:Oligopeptides; D019151:Peptide Library; C119235:lysyl-lysyl-valyl-valyl-phenylalanyl-lysyl-valyl-lysyl-phenylalanyl-lysine