Substitution at the 8-position of 3''-deoxy-cyclic ADP-carbocyclic-ribose, a highly potent Ca2+-mobilizing agent, provides partial agonists.
We previously showed that 3''-deoxy-cyclic ADP-carbocyclic-ribose (3''-deoxy-cADPcR, 4) is a stable and highly potent analogue of cyclic ADP-ribose (cADPR, 1), a Ca(2+)-mobilizing second messenger. From these results, we designed and synthesized other 3''-modified analogues of cADPcR having a substituent at the 8-position and found that this modification at the 8-position made them partial agonists. Among these compounds, 8-NH(2)-3''-deoxy-cADPcR (10) was identified as a potent partial agonist with an EC(50) value of 17 nM.
Kudoh
Takashi
T
Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.
Murayama
Takashi
T
Matsuda
Akira
A
Shuto
Satoshi
S
D000818:Animals; D002118:Calcium / Q000819:agonists*; D036563:Cyclic ADP-Ribose / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007202:Indicators and Reagents; D010063:Ovum / Q000378:metabolism; D012617:Sea Urchins; D016339:Spectrometry, Mass, Fast Atom Bombardment; D013056:Spectrophotometry, Ultraviolet; D013329:Structure-Activity Relationship
C514989:3''-deoxy-cyclic ADP-carbocyclic-ribose; D007202:Indicators and Reagents; D036563:Cyclic ADP-Ribose; D002118:Calcium