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Improved antimicrobial activity of h‐lysozyme (107–115) by rational Ala substitution
Author(s) -
González Rodrigo,
Albericio Fernando,
Cascone Osvaldo,
Iannucci Nancy B.
Publication year - 2010
Publication title -
journal of peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 66
eISSN - 1099-1387
pISSN - 1075-2617
DOI - 10.1002/psc.1258
Subject(s) - antimicrobial , lysozyme , peptide , escherichia coli , chemistry , antimicrobial peptides , staphylococcus aureus , residue (chemistry) , biochemistry , combinatorial chemistry , amino acid , rational design , antibiotics , bacteria , microbiology and biotechnology , biology , organic chemistry , genetics , gene
The most challenging target in the design of new antimicrobial agents is the development of antibiotic resistance. Antimicrobial peptides are good candidates as lead compounds for the development of novel anti‐infective drugs. Here we propose the sequential substitution of each Ala residue present in a lead peptide with known antimicrobial activity by specific amino acids, rationally chosen, that could enhance the activity of the resultant peptide. Taking the fragment 107–115 of the human lysozyme as lead, two‐round screening by sequentially replacing both Ala residues (108 and 111) by distinct amino acids resulted in a novel peptide with 4‐ and 20‐fold increased antimicrobial activity against Escherichia coli ATCC 25922 and Staphylococcus aureus ATCC 29213, respectively. These results reinforce the strategy proposed, which, in combination with simple and easy screening tools, will contribute to the rapid development of new therapeutic peptides required by the market. Copyright © 2010 European Peptide Society and John Wiley & Sons, Ltd.