Synthesis and biological activity of cyclic ADP-carbocyclic-ribose analogs: structure-activity relationship and conformational analysis of N-1-carbocyclic-ribose moiety.
Several cyclic ADP-carbocyclic-ribose analogs 3-10 modified in the N-1-carbocyclic-ribose moiety were synthesized. Their Ca2+-releasing activity was estimated in sea urchin eggs to show that the 3"-deoxy analog 6 shows 5 times more potent activity than cADPcR, but the 2",3"-didieoxy-2",3"-unsunsaturated analog 3 has very weak activity. We also calculated their stable conformation and found that 3 and 6 were significantly different in their stable conformation.
Kudoh
Takashi
T
Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
Fukuoka
Masayoshi
M
Shuto
Satoshi
S
Matsuda
Akira
A
D000244:Adenosine Diphosphate / Q000737:chemistry; D000818:Animals; D002118:Calcium / Q000378:metabolism; D036563:Cyclic ADP-Ribose / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008956:Models, Chemical; D008958:Models, Molecular; D008967:Molecular Biology / Q000379:methods; D008968:Molecular Conformation; D011487:Protein Conformation; D012266:Ribose / Q000737:chemistry*; D012617:Sea Urchins; D013329:Structure-Activity Relationship
C439996:cyclic ADP-carbocyclic-ribose; D036563:Cyclic ADP-Ribose; D000244:Adenosine Diphosphate; D012266:Ribose; D002118:Calcium