دورية أكاديمية
Structural determinants for N1/N7 cyclization of nicotinamide hypoxanthine 5'-dinucleotide (NHD+) derivatives by ADP-ribosyl cyclase from aplysia californica: Ca2+-mobilizing activity of 8-substituted cyclic inosine 5'-diphosphoribose analogues in T-lymphocytes.
| العنوان: | Structural determinants for N1/N7 cyclization of nicotinamide hypoxanthine 5'-dinucleotide (NHD+) derivatives by ADP-ribosyl cyclase from aplysia californica: Ca2+-mobilizing activity of 8-substituted cyclic inosine 5'-diphosphoribose analogues in T-lymphocytes. |
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| المؤلفون: | Moreau C; Wolfson Laboratory of Medicinal Chemistry, Department of Pharmacy and Pharmacology, University of Bath, Claverton Down, Bath, BA2 7AY, United Kingdom., Wagner GK, Weber K, Guse AH, Potter BV |
| المصدر: | Journal of medicinal chemistry [J Med Chem] 2006 Aug 24; Vol. 49 (17), pp. 5162-76. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Chemical Society Country of Publication: United States NLM ID: 9716531 Publication Model: Print Cited Medium: Print ISSN: 0022-2623 (Print) Linking ISSN: 00222623 NLM ISO Abbreviation: J Med Chem Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Washington Dc : American Chemical Society Original Publication: [Easton, Pa.] : American Chemical Society, [c1963- |
| مواضيع طبية MeSH: | ADP-ribosyl Cyclase/*chemistry , Aplysia/*enzymology , Calcium/*metabolism , Cyclic IMP/*pharmacology , Inosine Diphosphate/*chemical synthesis , T-Lymphocytes/*drug effects, Animals ; Cyclic IMP/chemical synthesis ; Cyclic IMP/chemistry ; Cyclization ; Humans ; Hydrolysis ; Inosine Diphosphate/chemistry ; Jurkat Cells ; Molecular Conformation ; Stereoisomerism ; Structure-Activity Relationship ; T-Lymphocytes/metabolism |
| مستخلص: | A series of nicotinamide hypoxanthine 5'-dinucleotide (NHD+) analogues modified at C-8 (2-5) and 7-deaza-NHD+ were synthesized, and cyclization in the presence of Aplysia ADP-ribosyl cyclase was studied. All 8-substituted NHD+ analogues were converted into their N1-cyclic forms by the enzyme, while in contrast, 7-deaza-NHD+ 17 was hydrolyzed into 7-deazainosine 5'-diphosphoribose (7-deaza-IDPR) 25. Correlations are made showing that the conformation of the NHD+ substrate is the key to successful cyclization. The pharmacological activities of these novel cIDPR derivatives were evaluated in both permeabilized and intact Jurkat T-lymphocytes. The results show that in permeabilized cells both 8-iodo 1g and 8-N3-N1-cIDPR 1d have an activity comparable to that of cADPR, while 8-iodo 1g and 8-phenyl-N1-cIDPR 1c have a small but significant effect in intact cells and can therefore be regarded as membrane-permeant; thus, cIDPR derivatives are emerging as important novel biological tools to study cADPR-mediated Ca2+ release in T-cells. |
| معلومات مُعتمدة: | 55709 United Kingdom Wellcome Trust |
| المشرفين على المادة: | 3545-76-4 (Cyclic IMP) 86-04-4 (Inosine Diphosphate) EC 3.2.2.5 (ADP-ribosyl Cyclase) SY7Q814VUP (Calcium) |
| تواريخ الأحداث: | Date Created: 20060818 Date Completed: 20061003 Latest Revision: 20131121 |
| رمز التحديث: | 20240628 |
| DOI: | 10.1021/jm060275a |
| PMID: | 16913705 |
| قاعدة البيانات: | MEDLINE |
Find this issue from the American Chemical Society | تدمد: | 0022-2623 |
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| DOI: | 10.1021/jm060275a |