Anti-microbial action of melanocortin peptides and identification of a novel X-Pro-D/L-Val sequence in Gram-positive and Gram-negative bacteria.
The melanocortin peptides alpha-MSH, Lys-Pro-Val and Lys-Pro-D-Val are known to be potent anti-inflammatory agents; however their role as antibacterial peptides is less clear. The aim of this study was to determine whether these peptides displayed antibacterial properties, and specifically whether the Lys-Pro-D-Val tripeptide was more potent than Lys-Pro-Val, consistent with their anti-inflammatory actions. alpha-MSH, Ac-Lys-Pro-D-Val-NH2 and Ac-Lys-Pro-Val-NH2 were found to be antibacterial against both Gram-positive and Gram-negative bacteria (Staphylococcus aureus and Escherichia coli) over a broad range of concentrations compared to a control peptide, Ac-Ala-Ala-Ala-NH2. However, the relative potency of alpha-MSH, Ac-Lys-Pro-D-Val-NH2, Ac-Lys-Pro-Val-NH2 did not differ. Furthermore, it was found that the cationic charge on the lysine residue was not required for activity as a variant peptide Ac-Ala-Pro-D-Val-NH2 was also antibacterial. We therefore describe a novel X-Pro-D/L-Val peptide sequence with similarity to the short melanocortin peptides, which possess antibacterial activity. The combined anti-inflammatory and antibacterial action of such peptides may also have potential value therapeutically.
Charnley
Mirren
M
Department of Engineering Materials, Kroto Research Institute, University of Sheffield, Sheffield S3 7HQ, UK.
Moir
Arthur J G
AJ
Douglas
C W Ian
CW
Haycock
John W
JW
D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D004151:Dipeptides / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli / Q000187:drug effects; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D006801:Humans; D053486:Melanocortins / Q000737:chemistry / Q000494:pharmacology*; D009074:Melanocyte-Stimulating Hormones / Q000737:chemistry / Q000378:metabolism; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology*; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D013211:Staphylococcus aureus / Q000187:drug effects; D013696:Temperature; D013997:Time Factors
D000900:Anti-Bacterial Agents; D004151:Dipeptides; D053486:Melanocortins; D009842:Oligopeptides; D010446:Peptide Fragments; C034446:prolylvaline; C043156:MSH (11-13); D009074:Melanocyte-Stimulating Hormones