jm501084q_si_001.pdf (6.02 MB)
Antimicrobial Peptides with Potential for Biofilm Eradication: Synthesis and Structure Activity Relationship Studies of Battacin Peptides
journal contribution
posted on 2015-01-22, 00:00 authored by Gayan
Heruka De Zoysa, Alan James Cameron, Veena V. Hegde, Srinivasarao Raghothama, Vijayalekshmi SarojiniWe
report on the first chemical syntheses and structure–activity
analyses of the cyclic lipopeptide battacin which revealed that conjugation
of a shorter fatty acid, 4-methyl-hexanoic acid, and linearization
of the peptide sequence improves antibacterial activity and reduces
hemolysis of mouse blood cells. This surprising finding of higher
potency in linear lipopeptides than their cyclic counterparts is economically
beneficial. This novel lipopeptide was membrane lytic and exhibited
antibiofilm activity against Pseudomonas aeruginosa, Staphylococcus aureus, and, for
the first time, Pseudomonas syringe pv. actinidiae. The peptide was unstructured in aqueous buffer and
dimyristoylphosphatidylcholine-polymerized diacetylene vesicles, with
12% helicity induced in 50% v/v of trifluoroethanol. Our results indicate
that a well-defined secondary structure is not essential for the observed
antibacterial activity of this novel lipopeptide. A truncated pentapeptide
conjugated to 4-methyl hexanoic acid, having similar potency against
Gram negative and Gram positive pathogens was identified through alanine
scanning.