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Synthetic Mimics of Antimicrobial Peptides with Immunomodulatory Responses

By Hitesh D. Thaker (1960867), Abhigyan Som (2065678), Furkan Ayaz (2065675), Dahui Lui (2065684), Wenxi Pan (2065681), Richard W. Scott (1912993), Juan Anguita (55227) and Gregory N. Tew (1264950)

Abstract

A new series of aryl-based synthetic mimics of antimicrobial peptides (SMAMPs) with antimicrobial activity and selectivity have been developed via systematic tuning of the aromatic groups and charge. The addition of a pendant aromatic group improved the antimicrobial activity against Gram-negative bacteria, while the addition of charge improved the selectivity. SMAMP <b>4</b> with six charges and a naphthalene central ring demonstrated a selectivity of 200 against both Staphylococcus aureus and Escherichia coli, compared with a selectivity of 8 for the peptide <b>MSI-78</b>. In addition to the direct antimicrobial activity, SMAMP <b>4</b> exhibited specific immunomodulatory activities in macrophages both in the presence and in the absence of lipopolysaccharide, a TLR agonist. SMAMP <b>4</b> also induced the production of a neutrophil chemoattractant, murine KC, in mouse primary cells. This is the first nonpeptidic SMAMP demonstrating both good antimicrobial and immunomodulatory activities

Topics: Biochemistry, Microbiology, Molecular Biology, Biotechnology, Immunology, Developmental Biology, Space Science, Environmental Sciences not elsewhere classified, Biological Sciences not elsewhere classified, Chemical Sciences not elsewhere classified, selectivity, MSI, KC, SMAMP 4, charge, TLR, peptide, antimicrobial activity, immunomodulatory activities
Year: 2012
DOI identifier: 10.1021/ja303304j.s001
OAI identifier: oai:figshare.com:article/2505820
Provided by: FigShare
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