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Proton magnetic resonance spectroscopic analysis of diadenosine 5′,5‴‐polyphosphates
Author(s) -
Mayo Kevin H.,
Mvele Omer M.,
Puri Rajinder N.
Publication year - 1990
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(90)80892-m
Subject(s) - polyphosphate , chemistry , ribose , adenosine , stereochemistry , ring (chemistry) , chemical shift , proton , phosphate , base (topology) , stacking , adenosine diphosphate , crystallography , proton nmr , nucleotide , resonance (particle physics) , enzyme , biochemistry , platelet aggregation , platelet , organic chemistry , mathematical analysis , physics , mathematics , quantum mechanics , gene , immunology , biology , particle physics
Certain diadenosine 5′,5‴‐polyphosphates are potent inhibitors of ADP stimulated platelet aggregation, acting possibly via competitive ADP‐receptor binding. 1 H NMR studies of a series of such compounds where the number of phosphate groups between adenosine groups was varied from 2 to 6 were performed to analyze possible preferred solution conformations and to define structure‐activity relations. Relative to mononucleotides ADP and ATP, chemical shifts of adenosine proton resonances in diadenosine polyphosphate analogs are upfield shifted suggesting base stacking. This effect is greatest for AP2A and AP3A. Coupling constants of ribose ring proton resonances support the idea of an anti‐base‐ribose ring conformation, and 3 J H5'‐P values suggest a preferred gauche H‐C‐O‐P structure. In all cases, NMR parameters for AP2A are near‐limiting values for a static base stacked conformation. Increasing the number of phosphate groups between adenosine moieties tends to weaken this interaction.