Document Detail


Nicotinic acid adenine dinucleotide phosphate analogues containing substituted nicotinic acid: effect of modification on Ca(2+) release.
MedLine Citation:
PMID:  20942470     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Pooja Jain; James T Slama; Leroy A Perez-Haddock; Timothy F Walseth
Publication Detail:
Type:  In Vitro; Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Journal of medicinal chemistry     Volume:  53     ISSN:  1520-4804     ISO Abbreviation:  J. Med. Chem.     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-11-04     Completed Date:  2010-12-28     Revised Date:  2014-09-08    
Medline Journal Info:
Nlm Unique ID:  9716531     Medline TA:  J Med Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  7599-612     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
ADP-ribosyl Cyclase / 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:
DA11806/DA/NIDA NIH HHS; P50 DA011806/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:
0/Calcium Channel Agonists; 0/Calcium Channel Blockers; 0/Calcium Channels; 53-59-8/NADP; 5502-96-5/NAADP; 59-67-6/Niacin; EC 3.2.2.5/ADP-ribosyl Cyclase; EC 3.2.2.5/NAD+ Nucleosidase; SY7Q814VUP/Calcium
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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