ja303304j_si_001.pdf (372.1 kB)
Synthetic Mimics of Antimicrobial Peptides with Immunomodulatory Responses
journal contribution
posted on 2012-07-11, 00:00 authored by Hitesh
D. Thaker, Abhigyan Som, Furkan Ayaz, Dahui Lui, Wenxi Pan, Richard
W. Scott, Juan Anguita, Gregory N. TewA 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 4 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 MSI-78. In addition to the direct antimicrobial
activity, SMAMP 4 exhibited specific immunomodulatory
activities in macrophages both in the presence and in the absence
of lipopolysaccharide, a TLR agonist. SMAMP 4 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.