Synthetic mimics of antimicrobial peptides with immunomodulatory responses.
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 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.
Department of Polymer Science and Engineering, University of Massachusetts, Amherst, Massachusetts 01003, USA.
Hitesh D
HD
Thaker
Abhigyan
A
Som
Furkan
F
Ayaz
Dahui
D
Lui
Wenxi
W
Pan
Richard W
RW
Scott
Juan
J
Anguita
Gregory N
GN
Tew
D000818:Animals; D000890:Anti-Infective Agents / Q000737:chemistry* / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry* / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects*; D040761:Biomimetic Materials / Q000737:chemistry* / Q000494:pharmacology; D002460:Cell Line; D004926:Escherichia coli / Q000187:drug effects; D004927:Escherichia coli Infections / Q000188:drug therapy; D007155:Immunologic Factors / Q000737:chemistry* / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D008958:Models, Molecular; D013203:Staphylococcal Infections / Q000188:drug therapy; D013211:Staphylococcus aureus / Q000187:drug effects
D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D007155:Immunologic Factors