|
KMID : 0578320110310010049
|
|
Molecules and Cells
2011 Volume.31 No. 1 p.49 ~ p.54
|
|
|
Activity Optimization of an Undecapeptide Analogue Derived from a Frog-Skin Antimicrobial Peptide
|
|
Won Hyung-Sik
Kang Su-Jin
Choi Wahn-Soo
Lee Bong-Jin
|
|
|
Abstract
|
|
|
|
While natural antimicrobial peptides are potential thera-peutic agents, their physicochemical properties and bioactivity generally need to be enhanced for clinical and commercial development. We have previously developed a cationic, amphipathic α-helical, 11-residue peptide (named herein GA-W2: FLGWLFKWASK-NH2) with potent antimicrobial and hemolytic activity, which was derived from a 24-residue, natural antimicrobial peptide isolated from frog skin. Here, we attempted to optimize peptide bioactivity by a rational approach to sequence modification. Seven analogues were generated from GA-W2, and their activities were compared with that of a 12-residue peptide, omiganan, which is being developed for clinical and commercial applications. Most of the modifications reported here improved antimicrobial activity. Among them, the GA-K4AL (FAKWAFKWLKK-NH2) peptide displayed the most potent antimicrobial activity with negligible hemolytic activity, superior to that of omiganan. The therapeutic index of GA-K4AL was improved more than 53- and more than 31-fold against Gram-negative and Gram-positive bacteria, respectively, compared to that of the starting peptide, GA-W2. Given its relatively shorter length and simpler amino acid composition, our sequence-optimized GA-K4AL peptide may thus be a potentially useful antimicrobial peptide agent.
|
|
|
KEYWORD
|
|
|
activity optimization, amphipathic helix, antimicrobial activity, antimicrobial peptide, hemolytic activity, sequence modification
|
|
|
FullTexts / Linksout information
|
|
|
|
|
|
Listed journal information
|
|
  
|
|