| Project/Area Number |
01570139
|
|---|
| Research Category |
Grant-in-Aid for General Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
General medical chemistry
|
|---|
| Research Institution | Kyushu University |
|---|
Principal Investigator |
HIRATA Masato Kyushu University. Faculty of Dentistry. Associate Professor, 歯学部, 助教授 (60136471)
|
|---|
| Project Period (FY) |
1989 – 1990
|
| Project Status |
Completed (Fiscal Year 1990)
|
| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1990: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1989: ¥1,000,000 (Direct Cost: ¥1,000,000)
|
|---|
| Keywords | IP_3 analogs / IP_3 phosphatase / IP_3 kinase / IP_3 receptor / Ca^<2+> ion / IP_3 affinity column / 光親和性標識 |
|---|
| Research Abstract |
A series of inositol 1.4.5-trisphosphate (IP_3) analogs, with a bulky substituent on the 2nd carbon of the inositol ring, has been synthesized and examined to explore the structure-activity relationships among IP_3-5-phosphatase. IP_3-3-kinase, and IP_3 binding protein. All analogs (racemic mixtures) inhibited the hydrolysis of [^3H] IP_3 catalyzed by erythrocyte ghosts. With a lower Ki value than seen with IP_3. The effective enantiomer in this process was found to be L-type. The analogs were capable of inhibiting the phosphorylation of [^3H] IP_3 to [^3H] IP_4 by brain cytosol. Although higher concentrations than IP_3 were required. By lowering free Ca^<2+>, the concentrations required for the inhibition became low. In this reaction. the D-enantiomer was effective. The D-enantiomer of these compoundsalso inhibited the binding of [^3H] IP_3 to cerebellum microsomes, With the same potency as seen with IP_3. And they acted as a full agonists in releasing Ca^<2+> from permeabilized macrophages. These results indicate that the 2nd position of IP_3 can be modified with only minor reduction in potency in several assay systems. Thus, the IP_3 analogs synthesized here may be linked to other molecules without loss of their biological activities. For example, the IP_3 analogs were coupled with Sepharose 4B to make IP_3 affinity columns, and the columns were proved to be useful for purifying the IP_3-recognizing proteins.
|
