title: Combinatorial approach toward synthesis of small molecule libraries as bacterial transglycosylase inhibitors.
abstract: The development of iminocyclitol-based small molecule libraries against a bacterial TGase is described. An iminocyclitol was conjugated with a pyrophosphate mimic using either a 1,3-dipolar cycloaddition or reductive amination reaction, which was then condensed with a variety of lipophilic carboxylic acids in an amide bond coupling to generate a desired molecular library. With assistance of microtiter plate-based combinatorial chemistry and in situ screening, a potential inhibitor, the first potent iminocyclitol-based inhibitor against bacterial TGases was efficiently developed.
authors.affiliation: Genomics Research Center, Academia Sinica, No. 128, Academia Road Sec. 2, Nankang District, Taipei, 11529, Taiwan.
authors.forename: Hao-Wei
authors.initials: HW
authors.lastname: Shih
authors.forename: Kuo-Ting
authors.initials: KT
authors.lastname: Chen
authors.forename: Shao-Kang
authors.initials: SK
authors.lastname: Chen
authors.forename: Chia-Ying
authors.initials: CY
authors.lastname: Huang
authors.forename: Ting-Jen R
authors.initials: TJ
authors.lastname: Cheng
authors.forename: Che
authors.initials: C
authors.lastname: Ma
authors.forename: Chi-Huey
authors.initials: CH
authors.lastname: Wong
authors.forename: Wei-Chieh
authors.initials: WC
authors.lastname: Cheng
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry*; D001419:Bacteria / Q000201:enzymology*; D020650:Combinatorial Chemistry Techniques; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry*; D016695:Glycosyltransferases / Q000037:antagonists & inhibitors*; D015394:Molecular Structure; D054852:Small Molecule Libraries / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D054852:Small Molecule Libraries; D016695:Glycosyltransferases