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Comparative mode of action of novel hybrid peptide CS ‐1a and its rearranged amphipathic analogue CS ‐2a
Author(s) -
Joshi Seema,
Bisht Gopal S.,
Rawat Diwan S.,
Maiti Souvik,
Pasha Santosh
Publication year - 2012
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.1742-4658.2012.08738.x
Subject(s) - peptide , amphiphile , mode of action , chemistry , action (physics) , stereochemistry , microbiology and biotechnology , biophysics , biochemistry , physics , biology , organic chemistry , copolymer , polymer , quantum mechanics
Cell selective, naturally occurring, host defence cationic peptides present a good template for the design of novel peptides with the aim of achieving a short length with improved antimicrobial potency and selectivity. A novel, short peptide CS ‐1a (14 residues) was derived using a sequence hybridization approach on sarcotoxin I (39 residues) and cecropin B (35 residues). The sequence of CS ‐1a was rearranged to enhance amphipathicity with the help of a S chiffer– E dmundson diagram to obtain CS ‐2a. Both peptides showed good antibacterial activity in the concentration range 4–16 μg· mL −1 against susceptible as well as drug‐resistant bacterial strains, including the clinically relevant pathogens A cenatobacter sp. and methicillin‐resistant S taphylococcus aureus . The major thrust of these peptides is their nonhaemolytic activity against human red blood cells up to a high concentration of 512 μg· mL −1 . Compared to CS ‐1a, amphipathic peptide CS ‐2a showed a more pronounced α‐helical conformation, along with a better membrane insertion depth in bacterial mimic 1,2‐dipalmitoyl‐ sn ‐glycero‐3‐phosphocholine/1,2‐dipalmitoyl‐ sn ‐glycero‐3‐phospho‐(1′‐ rac ‐glycerol) small unilamellar vesicles. With equivalent lipid‐binding affinity, the two peptides assumed different pathways of membrane disruption, as demonstrated by calcein leakage and the results of transmission electron microscopy on model bacterial mimic large unilamellar vesicles. Extending the work from model membranes to intact E scherichia coli cells, differences in membrane perturbation were visible in microscopic images of peptide‐treated E . coli . The present study describes two novel short peptides with potent activity, cell selectivity and divergent modes of action that will aid in the future design of peptides with better therapeutic potential.