Synthetic melanocortins with antimicrobial activityWO 2010|081492
Synthetic melanocortins (8 amino acid peptides, chemically stable) with antimicrobial effects to treat infective disorders.
The widespread use of antibiotics has caused a growing problem of antimicrobial resistance in the community and in hospital settings. Both fungal and bacterial resistance to current therapies are observed, particularly in immunocompromised patients. The melanocortins are endogenous peptides that exert pleiotropic effects on the host. One of these molecules, α-melanocyte stimulating hormone (α-MSH), has antiinflammatory and antimicrobial action. However, the 13 amino acid natural peptide has a short half-life and is not selective for individual melanocortin receptors, and, therefore, is unsuitable for clinical use. Chemically stable synthetic derivatives with more selective activity are being developed by pharmaceutical industry. Based on recent observations, synthetic melanocortins could likewise form the basis for novel antimicrobial therapies
Structure-activity relation (SAR) studies on α-MSH-derived sequences were performed in order to design synthetic molecules with enhanced potency and broad spectrum of antimicrobial activity. Replacement of Gly10 in [DNal(2’)-7, Phe-12]-α-MSH(6-13) with several conventional and unconventional amino acids with different degrees of conformational rigidity allowed the discovery of two derivatives with potent antimicrobial activity. These synthetic peptides had anti-Candida properties, including azole-resistant Candida strains, and exerted killing activity against bacterial strains including gram-positive and gram-negative organisms.
Patent granted in Canada, Israel, USA, Japan, India, Europe.
- Catania Anna
- Bonino Ferruccio
- Grieco Paolo
- Novellino Paolo