Synthesis of cyclic adenosine 5'-diphosphate ribose analogues: a C2'endo/syn "southern" ribose conformation underlies activity at the sea urchin cADPR receptor.
Novel 8-substituted base and sugar-modified analogues of the Ca(2+) mobilizing second messenger cyclic adenosine 5'-diphosphate ribose (cADPR) were synthesized using a chemoenzymatic approach and evaluated for activity in sea urchin egg homogenate (SUH) and in Jurkat T-lymphocytes; conformational analysis investigated by (1)H NMR spectroscopy revealed that a C2'endo/syn conformation of the "southern" ribose is crucial for agonist or antagonist activity at the SUH-, but not at the T cell-cADPR receptor.
Wolfson Laboratory of Medicinal Chemistry, Department of Pharmacy and Pharmacology, University of Bath, Bath, UK BA2 7AY.
Christelle
C
Moreau
Gloria A
GA
Ashamu
Victoria C
VC
Bailey
Antony
A
Galione
Andreas H
AH
Guse
Barry V L
BV
Potter
D000818:Animals; D001048:Aplysia / Q000201:enzymology; D002118:Calcium / Q000378:metabolism; D036563:Cyclic ADP-Ribose / Q000031:analogs & derivatives / Q000138:chemical synthesis*; D008958:Models, Molecular; D008968:Molecular Conformation; D018047:Receptors, Purinergic P1 / Q000378:metabolism*; D012266:Ribose / Q000737:chemistry*; D012617:Sea Urchins / Q000378:metabolism*
D018047:Receptors, Purinergic P1; D036563:Cyclic ADP-Ribose; D012266:Ribose; D002118:Calcium