A novel protocol to accelerate dynamic combinatorial chemistry via isolation of ligand-target adducts from dynamic combinatorial libraries: a case study identifying competitive inhibitors of lysozyme.
A novel protocol based on size-exclusion chromatography (SEC) and MS was established to accelerate dynamic combinatorial chemistry (DCC) in this study. By isolating ligand-target adducts from the dynamic combinatorial library (DCL), ligands could be identified directly by MS after denaturation. Three new inhibitors for lysozyme were discovered by this SEC-MS protocol in a case study. Km Data for these new inhibitors was also determined.
School of Pharmaceutical Science, Nanjing University of Technology, Nanjing, China.
Zheng
Z
Fang
Wei
W
He
Xin
X
Li
Zhengjiang
Z
Li
Beining
B
Chen
Pingkai
P
Ouyang
Kai
K
Guo
D000818:Animals; D002645:Chickens; D020650:Combinatorial Chemistry Techniques; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008024:Ligands; D015394:Molecular Structure; D009113:Muramidase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D008024:Ligands; C421864:hen egg lysozyme; D009113:Muramidase
Combinatorial chemistry; Drug discovery; Enzyme inhibitors; Ligand separation