Analogues of cyclic adenosine 5'-diphosphate ribose and adenophostin A, nucleotides in cellular signal transduction.
Nicotinamide 8-Br-hypoxanthine dinucleotide (8-Br-NHD+) was cyclised at the N-1 position by ADP-ribosyl cyclase from Aplysia californica to give cyclic 8-Br-inosine diphosphoribose, a novel membrane-permeant analogue of cyclic-ADP ribose and agonist in human T cells. Adenine-substituted analogues of adenophostin A with potent Ca2+ releasing activity were synthesized; docking studies using the binding core of the Ins(1,4,5)P3 receptor identified specific residues that could be of importance in determining the hyperagonist nature of adenophostin activity.
D000241:Adenosine / Q000031:analogs & derivatives* / Q000737:chemistry*; D000818:Animals; D001048:Aplysia; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism; D036563:Cyclic ADP-Ribose / Q000031:analogs & derivatives* / Q000737:chemistry; D006801:Humans; D053496:Inositol 1,4,5-Trisphosphate Receptors; D009690:Nucleic Acid Conformation; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D015398:Signal Transduction
D015220:Calcium Channels; C506926:ITPR1 protein, human; D053496:Inositol 1,4,5-Trisphosphate Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D036563:Cyclic ADP-Ribose; C085029:adenophostin A; D000241:Adenosine; D002118:Calcium