TY - JOUR
T1 - Novel α-MSH Peptide Analogues with Broad Spectrum Antimicrobial Activity
AU - Grieco, Paolo
AU - Carotenuto, Alfonso
AU - Auriemma, Luigia
AU - Limatola, Antonio
AU - Di Maro, Salvatore
AU - Merlino, Francesco
AU - Mangoni, Maria Luisa
AU - Luca, Vincenzo
AU - Di Grazia, Antonio
AU - Gatti, Stefano
AU - Campiglia, Pietro
AU - Gomez-Monterrey, Isabel
AU - Novellino, Ettore
AU - Catania, Anna
PY - 2013/4/23
Y1 - 2013/4/23
N2 - 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 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 α-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.
AB - 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 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 α-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.
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U2 - 10.1371/journal.pone.0061614
DO - 10.1371/journal.pone.0061614
M3 - Article
C2 - 23626703
AN - SCOPUS:84876568118
VL - 8
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 4
M1 - e61614
ER -