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Disruption of Interactions between Hydrophobic Residues on Nonpolar Faces is a Key Determinant in Decreasing Hemolysis and Increasing Antimicrobial Activities of α‐Helical Amphipathic Peptides
Author(s) -
Son Mieon,
Lee Yuri,
Hwang Heeyong,
Hyun Soonsil,
Yu Jaehoon
Publication year - 2013
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201300264
Subject(s) - amphiphile , antimicrobial , hemolysis , antimicrobial peptides , chemistry , membrane , peptide , combinatorial chemistry , biochemistry , computational biology , stereochemistry , biology , organic chemistry , copolymer , immunology , polymer
To design antimicrobial peptides with decrease pore‐forming activity in eukaryotic (host) membranes, an amphipathic α‐helical model peptide composed of Leu and Lys was modified to probe the balance in antimicrobial and hemolytic activities. Among analogues with broken hydrophobic interactions, L8N derivative exhibited an 8000‐fold decrease in hemolytic activity and an eightfold improvement in antimicrobial activity, affording a 64 000‐fold increase in therapeutic index against E. coli.