Combinatorial approach toward synthesis of small molecule libraries as bacterial transglycosylase inhibitors.
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.
Shih
Hao-Wei
HW
Genomics Research Center, Academia Sinica, No. 128, Academia Road Sec. 2, Nankang District, Taipei, 11529, Taiwan.
Chen
Kuo-Ting
KT
Chen
Shao-Kang
SK
Huang
Chia-Ying
CY
Cheng
Ting-Jen R
TJ
Ma
Che
C
Wong
Chi-Huey
CH
Cheng
Wei-Chieh
WC
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
D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D054852:Small Molecule Libraries; D016695:Glycosyltransferases