The Acyl Group as the Central Element of the Structural Organization of Antimicrobial Lipopeptide

Incorporation of an acyl chain into the peptides extends their range of activities. In known lipopeptide structures the peptide and non-peptidyl segment are segregated into two separate structural domains. Solution NMR conformation of the cationic antimicrobial lipopeptide C12LF11 (N-lauryl undecapeptide LF11 based on human lactoferrin) shows a completely reorganized peptide conformation in micellar environment in comparison to the parent peptide. As a striking difference to other known lipopeptide structures, the acyl chain of C12LF11 forms an integral part of the hydrophobic cluster with long-range effects on the peptide conformation. The peptide C-terminus forms two helical segments and is better defined in DPC than in SDS micelles. Peptide acylation improved particularly the activity against the bacterial strains with short oligosaccharide (rough) LPS chemotype and protected mice against the endotoxic shock. The profound structural effects of acylation demonstrate that this type of modification allows a manipulation of the peptide's conformation and improves their bioactivity.