title: Expedient Synthesis of SMAMPs via Click Chemistry.
abstract: A novel series of synthetic mimics of antimicrobial peptides (SMAMPs) containing triazole linkers were assembled using click chemistry. While only moderately active in buffer alone, an increase in antimicrobial activity against Staphylococcus aureus and Escherichia coli was observed when these SMAMPs were administered in the presence of mouse serum. One compound had minimum inhibitory concentrations (MICs) of 0.39 μg/mL and 6.25 μg/mL, respectively, and an HC50 of 693 μg/mL. These values compared favorably to peptide-based antimicrobials. A correlation between the net positive charge and SMAMP antimicrobial activity was observed. The triazole linker, an amide surrogate, was found to provide better antimicrobial activity against both S. aureus and E. coli when compared to other analogues.
authors.affiliation: Polymer Science and Engineering Department, University of Massachusetts , 120 Governors Drive, Amherst, Massachusetts 01003, United States.
authors.forename: Tsung-Hao
authors.initials: TH
authors.lastname: Fu
authors.affiliation: Polymer Science and Engineering Department, University of Massachusetts , 120 Governors Drive, Amherst, Massachusetts 01003, United States.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Polymer Science and Engineering Department, University of Massachusetts , 120 Governors Drive, Amherst, Massachusetts 01003, United States.
authors.forename: Hitesh D
authors.initials: HD
authors.lastname: Thaker
authors.affiliation: PolyMedix, Inc. , 170 North Radnor-Chester Road, Suite 300, Radnor, Pennsylvania 19087, United States.
authors.forename: Richard W
authors.initials: RW
authors.lastname: Scott
authors.affiliation: Polymer Science and Engineering Department, University of Massachusetts , 120 Governors Drive, Amherst, Massachusetts 01003, United States.
authors.forename: Gregory N
authors.initials: GN
authors.lastname: Tew
keywords: 1,2,3-triazoles; Gram-positive and Gram-negative bacteria; Synthetic mimics of antimicrobial peptides; antibiotics; click chemistry