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Design, Synthesis and SAR Studies of NAD Analogues as Potent Inhibitors towards CD38 NADase

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′-fluoroarabin...

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Detalles Bibliográficos
Autores principales: Wang, Shengjun, Zhu, Wenjie, Wang, Xuan, Li, Jianguo, Zhang, Kehui, Zhang, Liangren, Zhao, Yong-Juan, Lee, Hon Cheung, Zhang, Lihe
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6271716/
https://www.ncbi.nlm.nih.gov/pubmed/25268725
http://dx.doi.org/10.3390/molecules191015754
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author Wang, Shengjun
Zhu, Wenjie
Wang, Xuan
Li, Jianguo
Zhang, Kehui
Zhang, Liangren
Zhao, Yong-Juan
Lee, Hon Cheung
Zhang, Lihe
author_facet Wang, Shengjun
Zhu, Wenjie
Wang, Xuan
Li, Jianguo
Zhang, Kehui
Zhang, Liangren
Zhao, Yong-Juan
Lee, Hon Cheung
Zhang, Lihe
author_sort Wang, Shengjun
collection PubMed
description 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-nicotinamideguanine dinucleotide (ara-F NGD) was the most effective one. The structure-activity relationship of NAD analogues was also discussed.
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spelling pubmed-62717162018-12-27 Design, Synthesis and SAR Studies of NAD Analogues as Potent Inhibitors towards CD38 NADase Wang, Shengjun Zhu, Wenjie Wang, Xuan Li, Jianguo Zhang, Kehui Zhang, Liangren Zhao, Yong-Juan Lee, Hon Cheung Zhang, Lihe Molecules Article 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-nicotinamideguanine dinucleotide (ara-F NGD) was the most effective one. The structure-activity relationship of NAD analogues was also discussed. MDPI 2014-09-29 /pmc/articles/PMC6271716/ /pubmed/25268725 http://dx.doi.org/10.3390/molecules191015754 Text en © 2014 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Wang, Shengjun
Zhu, Wenjie
Wang, Xuan
Li, Jianguo
Zhang, Kehui
Zhang, Liangren
Zhao, Yong-Juan
Lee, Hon Cheung
Zhang, Lihe
Design, Synthesis and SAR Studies of NAD Analogues as Potent Inhibitors towards CD38 NADase
title Design, Synthesis and SAR Studies of NAD Analogues as Potent Inhibitors towards CD38 NADase
title_full Design, Synthesis and SAR Studies of NAD Analogues as Potent Inhibitors towards CD38 NADase
title_fullStr Design, Synthesis and SAR Studies of NAD Analogues as Potent Inhibitors towards CD38 NADase
title_full_unstemmed Design, Synthesis and SAR Studies of NAD Analogues as Potent Inhibitors towards CD38 NADase
title_short Design, Synthesis and SAR Studies of NAD Analogues as Potent Inhibitors towards CD38 NADase
title_sort design, synthesis and sar studies of nad analogues as potent inhibitors towards cd38 nadase
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6271716/
https://www.ncbi.nlm.nih.gov/pubmed/25268725
http://dx.doi.org/10.3390/molecules191015754
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