Nicotinic acid adenine dinucleotide phosphate analogues containing substituted nicotinic acid: effect of modification on Ca(2+) release.

Nicotinic acid adenine dinucleotide phosphate analogues containing substituted nicotinic acid: effect of modification on Ca(2+) release.
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DOI:
10.1021/jm1007209
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发表时间:
2010-11-11
影响因子:
7.3
通讯作者:
Walseth TF
Walseth TF
中科院分区:
医学1区
文献类型:
--
作者:
Jain P;Slama JT;Perez-Haddock LA;Walseth TF

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以烟酸腺嘌呤二核苷酸磷酸(NAADP)为原料,利用Aplysia calfornica ADP-核糖环化酶或哺乳动物NAD糖水解酶,在烟酸部分的4位或5位进行取代,合成了烟酸二核苷酸类似物。烟酸的4位取代导致海胆卵匀浆中钙离子释放的激动剂活性丧失,以及[~(32)P]NAADP竞争配体结合分析的活性丧失。相反,几个5-取代的NAADP衍生物表现出很高的结合活性和完全的钙释放激动剂活性。5-叠氮基-NAADP在低浓度下能从海胆卵匀浆中释放钙,并与[~(32)P]NAADP竞争结合,IC50为18 nM,表明该化合物可能是一种潜在的光探针,可用于NAADP受体的特异性标记和鉴定。
Analogs 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 Ca2+-ions from sea urchin egg homogenates and in potency for competition ligand binding assays using [32P]NAADP. In contrast, several 5-substituted NAADP derivatives showed high potency for binding and full agonist activity for Ca2+ release. 5-Azido-NAADP was shown to release calcium from sea urchin egg homogenates at low concentration and to compete with [32P]NAADP in a competition ligand binding assay with an IC50 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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