First enzymatic synthesis of an N1-cyclised cADPR (cyclic-ADP ribose) analogue with a hypoxanthine partial structure: discovery of a membrane permeant cADPR agonist.
Nicotinamide 8-Br-hypoxanthine dinucleotide (8-Br-NHD+) was cyclised at the N1 position by the ADP-ribosyl cyclase from Aplysia californica to give cyclic 8-Br-inosine diphosphoribose (8-Br-N1-cIDPR), a novel membrane-permeant agonist of Ca2+ release in human T cells.
Wagner
Gerd K
GK
University of Bath, Department of Pharmacy and Pharmacology, Wolfson Laboratory of Medicinal Chemistry, Claverton Down, Bath, UK BA2 7AY.
Black
Steven
S
Guse
Andreas H
AH
Potter
Barry V L
BV
D036541:ADP-ribosyl Cyclase / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D003300:Copper / Q000494:pharmacology; D036563:Cyclic ADP-Ribose / Q000031:analogs & derivatives* / Q000096:biosynthesis* / Q000737:chemistry; D006801:Humans; D019271:Hypoxanthine / Q000378:metabolism*; D019169:Jurkat Cells / Q000187:drug effects / Q000378:metabolism
D036563:Cyclic ADP-Ribose; D019271:Hypoxanthine; D003300:Copper; D036541:ADP-ribosyl Cyclase