Transition State-Based Sialyltransferase Inhibitors: Mimicking Oxocarbenium Ion by Simple Amide.
In the new transition-state based sialyltransferase inhibitors, an amide group was placed at the corresponding C-2 position of CMP-sialic acid to mimic the geometry and charge distribution in the transition state, and simple aromatic or aliphatic rings were used instead of the sialic acid moiety. All synthetic compounds exhibited excellent α(2-6)-sialyltransferase inhibition, resulting in up to a 2600-fold higher affinity for the enzyme than CMP-Neu5Ac, suggesting that amide is a key element for simulating transition-state features.
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University , Xue Yuan Road no. 38, Beijing 100191, China.
Jian
J
Guo
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University , Xue Yuan Road no. 38, Beijing 100191, China.
Wenming
W
Li
School of Pharmaceutical Sciences and Innovative Drug Research Centre, Chongqing University , Daxuecheng South Road no. 55, Chongqing 401331, China.
Weiwei
W
Xue
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University , Xue Yuan Road no. 38, Beijing 100191, China.
Xin-Shan
0000-0003-4113-506X
XS
Ye
D000577:Amides / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D012799:Sialyltransferases / Q000037:antagonists & inhibitors*; D013056:Spectrophotometry, Ultraviolet
D000577:Amides; D004791:Enzyme Inhibitors; D012799:Sialyltransferases