A novel synthetic peptide derivative from lactoferrin exhibiting antimicrobial activity

A tetrapeptide derivative Boc-L-Lys(Boc)-L-Arg-L-Asp-L-Ser(But)-OBut (PEP 1261; Boc is butoxycarbonyl, Bu^t is t-butyl and OBu^t is t-butyl ester), synthesized by a solution-phase strategy, exhibited antimicrobial activity against a broad spectrum of micro-organisms at an optimal concentration of 500 mg/ml. Whereas the tetrapeptide salt (L-Lys-L-Arg-L-Asp-L-Ser·HCl) was found to be fairly effective against bacterial cultures, it was not effective against fungal cultures. Comparative growth studies showed that PEP 1261 was equally as potent as the conventional antibiotics kanamycin, streptomycin and actidione for the Gram-negative bacteria Escherichia coli, Pseudomonas alcaligenes and the non-filamentous fungus Saccharomyces cerevisiae (bakerʹs yeast), whereas 62 and 88.9% inhibition were observed for Gram-positive organisms such as Staphylococcus aureus and Bacillus thuringiensis respectively. PEP 1261 might exert its antimicrobial activity by permeabilizing the bacterial membrane, and this was confirmed by an increase in b-galactosidase activity.