Biomimetic facially amphiphilic antibacterial oligomers with conformationally stiff backbones.
A foldamer has been designed with a conformationally stiff backbone that is facially amphiphilic. The oligomer has excellent antimicrobial activity and was found to be 18 times more active toward bacterial cells than human red blood cells. The oligomer is built from arylamide bonds around a central 4,6-dicarboxy pyrimidine ring. The conformation was studied by X-ray crystallography and solution NMR spectroscopy. Density-functional (DFT) calculations were performed to guide the design. These calculations accurately predicted the overall conformation as well as NMR chemical shifts. Antibacterial activity was demonstrated against E. coli, a gram-negative strain, and B. subtilis, a gram-positive strain. The minimal inhibitory concentration is 0.8 microg/ml.
Tang
Haizhong
H
Polymer Science and Engineering Department, University of Massachusetts, 120 Governors Drive, Amherst, Massachusetts 01003, USA.
Doerksen
Robert J
RJ
Jones
Ticora V
TV
Klein
Michael L
ML
Tew
Gregory N
GN
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D001412:Bacillus subtilis / Q000187:drug effects; D018360:Crystallography, X-Ray; D015195:Drug Design; D004926:Escherichia coli / Q000187:drug effects; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D008958:Models, Molecular; D008968:Molecular Conformation; D018716:Molecular Mimicry; D015394:Molecular Structure
D000900:Anti-Bacterial Agents