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Novel ?-MSH peptide analogues with broad spectrum antimicrobial activity.

ABSTRACT: Previous investigations indicate that ?-melanocyte-stimulating hormone (?-MSH) and certain synthetic analogues of it exert antimicrobial effects against bacteria and yeasts. However, these molecules have weak activity in standard microbiology conditions and this hampers a realistic clinical use. The aim in the present study was to identify novel peptides with broad-spectrum antimicrobial activity in growth medium. To this purpose, the Gly10 residue in the [DNal(2')-7, Phe-12]-MSH(6-13) sequence was replaced with conventional and unconventional amino acids with different degrees of conformational rigidity. Two derivatives in which Gly10 was replaced by the residues Aic and Cha, respectively, had substantial activity against Candida strains, including C. albicans, C. glabrata, and C. krusei and against gram-positive and gram-negative bacteria. Conformational analysis indicated that the helical structure along residues 8-13 is a key factor in antimicrobial activity. Synthetic analogues of ?-MSH can be valuable agents to treat infections in humans. The structural preferences associated with antimicrobial activity identified in this research can help further development of synthetic melanocortins with enhanced biological activity.

SUBMITTER: Grieco P

PROVIDER: S-EPMC3634028 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Novel α-MSH peptide analogues with broad spectrum antimicrobial activity.

Grieco Paolo P Carotenuto Alfonso A Auriemma Luigia L Limatola Antonio A Di Maro Salvatore S Merlino Francesco F Mangoni Maria Luisa ML Luca Vincenzo V Di Grazia Antonio A Gatti Stefano S Campiglia Pietro P Gomez-Monterrey Isabel I Novellino Ettore E Catania Anna A

PloS one 20130423 4

Previous investigations indicate that α-melanocyte-stimulating hormone (α-MSH) and certain synthetic analogues of it exert antimicrobial effects against bacteria and yeasts. However, these molecules have weak activity in standard microbiology conditions and this hampers a realistic clinical use. The aim in the present study was to identify novel peptides with broad-spectrum antimicrobial activity in growth medium. To this purpose, the Gly10 residue in the [DNal(2')-7, Phe-12]-MSH(6-13) sequence ...[more]

PMID: 23626703

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Project description:Due to the wide etiology of conjunctivitis, the expensive and time-consuming diagnosis requires new therapeutic strategies with broad-spectrum antimicrobial activity and nonselective mechanisms of action. In this context, eye drops could provide an alternative to conventional antimicrobial therapies. Here, we compare the antibacterial and antiviral activity of Oftasecur and Visuprime, commercially available ophthalmic solutions. Cytotoxicity assay was performed on Vero CCL-81 cells by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) test. Antibacterial efficacy was evaluated on Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, Escherichia coli, and Klebsiella pneumoniae by disk diffusion, broth microdilution methods, and time-killing tests. Furthermore, the antiviral activity against HSV-1 was estimated by co-treatment, cell and viral pretreatment and post-treatment, via plaque reduction assay, fluorescence assessment (GFP-engineered HSV-1), and real-time PCR. After 24 h of exposure, Oftasecur and Visuprime showed a volume-inducing 50% of cytotoxicity of 125 and 15.8 μL, respectively Oftasecur and Visuprime induced 90% antibacterial activity in response to mean volume of 10.0 and 4.4 µL for Gram-positive and Gram-negative strains, respectively. Oftasecur exerted bactericidal action on both bacterial populations, while Visuprime was bacteriostatic on Gram-negative strains and slightly bactericidal on Gram-positive bacteria. A major impact on infectivity occurred by exposure of viral particles to the ophthalmic solutions. In detail, 50% of inhibition was verified by exposing the viral particles to 3.12 and 0.84 μL of Oftasecur and Visuprime, respectively, for 1 h. The reduction of the fluorescence and the expression of the viral genes confirmed the recorded antiviral activity. Due to their high antimicrobial efficiency, Oftasecur and Visuprime could represent a valid empirical strategy for the treatment of conjunctivitis.

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Novel ?-MSH peptide analogues with broad spectrum antimicrobial activity.

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Novel α-MSH peptide analogues with broad spectrum antimicrobial activity.

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