The chemical synthesis of cecropin D and an analog with enhanced antibacterial activity.
Cecropin D was synthesized by solid-phase methods and shown to be homogeneous and of correct composition and molecular weight. It was indistinguishable from natural cecropin D and constitutes a structure proof for this peptide. Several analogs of cecropin D were synthesized and used to draw conclusions about the structural features contributing to antibacterial activity. They included [Lys1]cecropin D, [Gln3, Leu4] cecropin D, and cecropin D-(9-37). It was concluded that a strongly basic NH2-terminal segment is a prerequisite for antibacterial activity. A hybrid analog cecropin A-(1-11) D-(12-37) was designed and predicted to have enhanced potency. It was found to be 5 to 55 times as active as cecropin D against six of the bacteria tested and was slightly more active than cecropin A. However, against Bacillus subtilis Bs11 the analog was 6 times more active than cecropin A.
Fink
J
J
Rockefeller University, New York, New York 10021.
Merrifield
R B
RB
Boman
A
A
Boman
H G
HG
D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis; D002851:Chromatography, High Pressure Liquid; D004492:Edetic Acid / Q000494:pharmacology; D004591:Electrophoresis, Polyacrylamide Gel; D004926:Escherichia coli / Q000187:drug effects; D007301:Insect Hormones / Q000138:chemical synthesis* / Q000633:toxicity; D019476:Insect Proteins; D008969:Molecular Sequence Data; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D007301:Insect Hormones; D019476:Insect Proteins; C036149:cecropin D protein, Hyalophora cecropia; D004492:Edetic Acid