| Nicotinic acid adenine dinucleotide phosphate analogues containing substituted nicotinic acid: effect of modification on Ca(2+) release. | |
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MedLine Citation:
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PMID: 20942470 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Analogues of nicotinic acid adenine dinucleotide phosphate (NAADP) with substitution at either the 4- or the 5-position position of the nicotinic acid moiety have been synthesized from NADP enzymatically using Aplysia californica ADP-ribosyl cyclase or mammalian NAD glycohydrolase. Substitution at the 4-position of the nicotinic acid resulted in the loss of agonist potency for release of Ca(2+)-ions from sea urchin egg homogenates and in potency for competition ligand binding assays using [(32)P]NAADP. In contrast, several 5-substituted NAADP derivatives showed high potency for binding and full agonist activity for Ca(2+) release. 5-Azido-NAADP was shown to release calcium from sea urchin egg homogenates at low concentration and to compete with [(32)P]NAADP in a competition ligand binding assay with an IC(50) of 18 nM, indicating that this compound might be a potential photoprobe useful for specific labeling and identification of the NAADP receptor. |
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Authors:
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Pooja Jain; James T Slama; Leroy A Perez-Haddock; Timothy F Walseth |
Publication Detail:
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Type: In Vitro; Journal Article; Research Support, N.I.H., Extramural |
Journal Detail:
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Title: Journal of medicinal chemistry Volume: 53 ISSN: 1520-4804 ISO Abbreviation: J. Med. Chem. Publication Date: 2010 Nov |
Date Detail:
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Created Date: 2010-11-04 Completed Date: 2010-12-28 Revised Date: 2011-11-21 |
Medline Journal Info:
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Nlm Unique ID: 9716531 Medline TA: J Med Chem Country: United States |
Other Details:
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Languages: eng Pagination: 7599-612 Citation Subset: IM |
Affiliation:
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Department of Medicinal and Biological Chemistry, College of Pharmacy, University of Toledo, Health Science Campus, MS no 1015, 3000 Arlington Avenue, Toledo, Ohio 43614, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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ADP-ribosyl Cyclase
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chemistry Animals Aplysia / enzymology Binding, Competitive Calcium / metabolism* Calcium Channel Agonists / chemical synthesis, pharmacology Calcium Channel Blockers / chemical synthesis, pharmacology Calcium Channels / metabolism NAD+ Nucleosidase / chemistry NADP / analogs & derivatives*, chemical synthesis, pharmacology Niacin / analogs & derivatives*, chemical synthesis*, pharmacology Radioligand Assay Sea Urchins Structure-Activity Relationship |
| Grant Support | |
ID/Acronym/Agency:
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DA11806/DA/NIDA NIH HHS; P50 DA011806-09/DA/NIDA NIH HHS; R25 HL088728/HL/NHLBI NIH HHS; R25 HL088728-01/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Calcium Channel Agonists; 0/Calcium Channel Blockers; 0/Calcium Channels; 53-59-8/NADP; 5502-96-5/NAADP; 59-67-6/Niacin; 7440-70-2/Calcium; EC 3.2.2.5/ADP-ribosyl Cyclase; EC 3.2.2.5/NAD+ Nucleosidase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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