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- Title
Design, Synthesis and SAR Studies of NAD Analogues as Potent Inhibitors towards CD38 NADase.
- Authors
Shengjun Wang; Wenjie Zhu; Xuan Wang; Jianguo Li; Kehui Zhang; Liangren Zhang; Yong-Juan Zhao; Hon Cheung Lee; Lihe Zhang
- 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.
- Subjects
NICOTINAMIDE adenine dinucleotide phosphate; CHEMICAL synthesis; RIBOSE; CALCIUM; COENZYMES; CYCLIC compounds
- Publication
Molecules, 2014, Vol 19, Issue 10, p15754
- ISSN
1420-3049
- Publication type
Article
- DOI
10.3390/molecules191015754