title: Design, synthesis and SAR studies of NAD analogues as potent inhibitors towards CD38 NADase.
abstract: Nicotinamide adenine dinucleotide (NAD), one of the most important coenzymes in the cells, is a substrate of the signaling enzyme CD38, by which NAD is converted to a second messenger, cyclic ADP-ribose, which releases calcium from intracellular calcium stores. Starting with 2'-deoxy-2'-fluoroarabinosyl-β-nicotinamide adenine dinucleotide (ara-F NAD), a series of NAD analogues were synthesized and their activities to inhibit CD38 NAD glycohydrolase (NADase) were evaluated. The adenosine-modified analogues showed potent inhibitory activities, among which 2'-deoxy-2'-fluoroarabinosyl-β-nicotinamide guanine dinucleotide (ara-F NGD) was the most effective one. The structure-activity relationship of NAD analogues was also discussed.
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China. wangshengjun@bjmu.edu.cn.
authors.forename: Shengjun
authors.initials: S
authors.lastname: Wang
authors.affiliation: School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen 518052, China. wilsonzwjdx@126.com.
authors.forename: Wenjie
authors.initials: W
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China. wangxuan0913@163.com.
authors.forename: Xuan
authors.initials: X
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China. lijianguo.08@163.com.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Li
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China. kehuizhang@bjmu.edu.cn.
authors.forename: Kehui
authors.initials: K
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China. liangren@bjmu.edu.cn.
authors.forename: Liangren
authors.initials: L
authors.lastname: Zhang
authors.affiliation: School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen 518052, China. zhaoyongjuan@gmail.com.
authors.forename: Yong-Juan
authors.initials: YJ
authors.lastname: Zhao
authors.affiliation: School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen 518052, China. leehoncheung@gmail.com.
authors.forename: Hon Cheung
authors.initials: HC
authors.lastname: Lee
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China. zdszlh@bjmu.edu.cn.
authors.forename: Lihe
authors.initials: L
authors.lastname: Zhang
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000037:antagonists & inhibitors / Q000737:chemistry*; D060326:Chemistry Techniques, Synthetic; D015195:Drug Design; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D006150:Guanine Nucleotides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D015394:Molecular Structure; D009243:NAD / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011485:Protein Binding; D013379:Substrate Specificity
chemical_list: D004791:Enzyme Inhibitors; D006150:Guanine Nucleotides; D009243:NAD; C102728:nicotinamide guanine dinucleotide; D051997:ADP-ribosyl Cyclase 1