TY - JOUR
T1 - Bicyclic analogues of D-myo-Inositol 1,4,5-trisphosphate related to adenophostin A
T2 - synthesis and biological activity
AU - Riley, Andrew M.
AU - Correa, Vanessa
AU - Mahon, Mary F.
AU - Taylor, Colin W.
AU - Potter, Barry V. L.
N1 - ID number: ISI:000169367000008
PY - 2001
Y1 - 2001
N2 - The high affinity of adenophostin A for 1D-myo-inositol 1,4,5-trisphosphate [Ins(1,4,5)P-3] receptors may be related to an alteration in the position of its 2'-phosphate group relative to the corresponding 1-phosphate group in Ins(1,4,5)P-3. To investigate this possibility, two bicyclic trisphosphates 9 and 10, designed to explore the effect of relocating the l-phosphate group of Ins(1,4,5)P-3 using a novel fused-ring system, were synthesized from myo-inositol. Biological evaluation of 9 and 10 at the Ins(1,4,5)P-3 receptors of hepatocytes showed that both were recognized by hepatic Ins(1,4,5)P-3 receptors and both stimulated release of Ca2+ from intracellular stores, but they had lower affinity than Ins(1,4,5)P-3. This finding may be explained by considering the three-dimensional structures of 9 and 10 in light of recent studies on the conformation of adenophostin A.
AB - The high affinity of adenophostin A for 1D-myo-inositol 1,4,5-trisphosphate [Ins(1,4,5)P-3] receptors may be related to an alteration in the position of its 2'-phosphate group relative to the corresponding 1-phosphate group in Ins(1,4,5)P-3. To investigate this possibility, two bicyclic trisphosphates 9 and 10, designed to explore the effect of relocating the l-phosphate group of Ins(1,4,5)P-3 using a novel fused-ring system, were synthesized from myo-inositol. Biological evaluation of 9 and 10 at the Ins(1,4,5)P-3 receptors of hepatocytes showed that both were recognized by hepatic Ins(1,4,5)P-3 receptors and both stimulated release of Ca2+ from intracellular stores, but they had lower affinity than Ins(1,4,5)P-3. This finding may be explained by considering the three-dimensional structures of 9 and 10 in light of recent studies on the conformation of adenophostin A.
UR - http://dx.doi.org/ 10.1021/jm0005499
U2 - 10.1021/jm0005499
DO - 10.1021/jm0005499
M3 - Article
SN - 0022-2623
VL - 44
SP - 2108
EP - 2117
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
IS - 13
ER -