'Click cyclic ADP-ribose': a neutral second messenger mimic.
Analogues of the potent Ca(2+) releasing second messenger cyclic ADP-ribose (cADPR) with a 1,2,3-triazole pyrophosphate bioisostere were synthesised by click-mediated macrocyclisation. The ability to activate Ca(2+) release was surprisingly retained, and hydrolysis of cADPR by CD38 could also be inhibited, illustrating the potential of this approach to design drug-like signalling pathway modulators.
Wolfson Laboratory of Medicinal Chemistry, Dept. of Pharmacy and Pharmacology, University of Bath, Bath, BA2 7AY, UK. B.V.L.Potter@bath.ac.uk.
Joanna M
JM
Swarbrick
Richard
R
Graeff
Clive
C
Garnham
Mark P
MP
Thomas
Antony
A
Galione
Barry V L
BV
Potter
D000818:Animals; D002118:Calcium / Q000378:metabolism; D057930:Click Chemistry; D036563:Cyclic ADP-Ribose / Q000737:chemistry* / Q000494:pharmacology; D011756:Diphosphates / Q000737:chemistry; D005260:Female; D010063:Ovum; D012617:Sea Urchins; D015290:Second Messenger Systems
D011756:Diphosphates; D036563:Cyclic ADP-Ribose; D002118:Calcium