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PLoS One. 2013 Sep 27;8(9):e77031. doi: 10.1371/journal.pone.0077031. eCollection 2013.

Effect of selectively introducing arginine and D-amino acids on the antimicrobial activity and salt sensitivity in analogs of human beta-defensins.

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1
CSIR-Centre for Cellular and Molecular Biology, Hyderabad, India.

Abstract

We have examined the antimicrobial activity of C-terminal analogs of human β-defensins HBD-1 and-3 wherein lysines have been selectively replaced by L- and D-arginines and L-isoleucine substituted with its D-enantiomer. The analogs exhibited antibacterial and antifungal activities. Physiological concentration of NaCl did not attenuate the activity of the peptides against Gram-negative bacteria considerably, while some attenuation of activity was observed against S. aureus. Variable attenuation of activity was observed in the presence of Ca²⁺ and Mg²⁺. Introduction of D-amino acids abrogated the need for a disulfide bridge for exhibiting activity. Confocal images of carboxyfluorescein (CF) labeled peptides indicated initial localization on the membrane and subsequent translocation into the cell. Analogs corresponding to cationic rich segments of human defensins substituted with L- and D-arginine, could be attractive candidates for development as future therapeutic drugs.

PMID:
24086767
PMCID:
PMC3785448
DOI:
10.1371/journal.pone.0077031
[Indexed for MEDLINE]
Free PMC Article
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