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Salt‐resistant homodimeric bactenecin, a cathelicidin‐derived antimicrobial peptide
Author(s) -
Lee Ju Y.,
Yang SungTae,
Lee Seung K.,
Jung Hyun H.,
Shin Song Y.,
Hahm KyungSoo,
Kim Jae I.
Publication year - 2008
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2008.06536.x
Subject(s) - dimer , chemistry , monomer , peptide , cathelicidin , antimicrobial , antimicrobial peptides , antiparallel (mathematics) , biophysics , stereochemistry , biochemistry , organic chemistry , biology , physics , quantum mechanics , magnetic field , polymer
The cathelicidin antimicrobial peptide bactenecin is a β‐hairpin molecule with a single disulfide bond and broad antimicrobial activity. The proform of bactenecin exists as a dimer, however, and it has been proposed that bactenecin is released as a dimer in vivo , although there has been little study of the dimeric form of bactenecin. To investigate the effect of bactenecin dimerization on its biological activity, we characterized the dimer’s effect on phospholipid membranes, the kinetics of its bactericidal activity, and its salt sensitivity. We initially synthesized two bactenecin dimers (antiparallel and parallel) and two monomers (β‐hairpin and linear). Under oxidative folding conditions, reduced linear bactenecin preferentially folded into a dimer forming a ladder‐like structure via intermolecular disulfide bonding. As compared to the monomer, the dimer had a greater ability to induce lysis of lipid bilayers and was more rapidly bactericidal. Interestingly, the dimer retained antimicrobial activity at physiological salt concentrations (150 m m NaCl), although the monomer was inactivated. This salt resistance was also seen with bactenecin dimer containing one intermolecular disulfide bond, and the bactenecin dimer appears to undergo multimeric oligomerization at high salt concentrations. Overall, dimeric bactenecin shows potent and rapid antimicrobial activity, and resists salt‐induced inactivation under physiological conditions through condensation and oligomerization. These characteristics shed light on the features that a peptide would need to serve as an effective therapeutic agent.