Design, synthesis and antibacterial activity of cecropin-like model peptides.
In order to investigate structure-activity relationships of cecropins, model peptides that mimic certain structural features of the cecropin molecules were designed and synthesized. The conformational analysis of cecropins and the design of the model peptides were based on Chou-Fasman calculations. The peptides were synthesized by solid-phase methods and purified by reverse-phase liquid-chromatography on C18-silica columns. Their secondary structures were studied by circular dichroism measurements. Antibacterial activities against seven test organisms were determined and compared to the activities of the natural cecropins A and B. These results were discussed on the basis of structural features of the model peptides and on model mechanisms. It was concluded that high antibacterial activity for this class of compounds requires a basic helical amphipathic N-terminal segment that is connected to a hydrophobic helical C-terminal segment by a flexible non-helical hinge region.
Fink
J
J
Rockefeller University, New York, New York.
Boman
A
A
Boman
H G
HG
Merrifield
R B
RB
D000595:Amino Acid Sequence; D002942:Circular Dichroism; D015195:Drug Design; D007301:Insect Hormones / Q000138:chemical synthesis* / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis* / Q000494:pharmacology; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D014270:Trifluoroethanol / Q000494:pharmacology
D007301:Insect Hormones; D010455:Peptides; D014270:Trifluoroethanol