1997 Fiscal Year Final Research Report Summary
Development and application of specific inhibitors for cyclin-dependent protein kinases on the basis of their substrate specificities.
| Project/Area Number |
08680634
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Bioorganic chemistry
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| Research Institution | Saga Medical School |
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Principal Investigator |
ANDO Shoji Saga Medical School, Chimistry Laboratory, Associate Professor, 医学部, 助教授 (20193104)
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| Project Period (FY) |
1996 – 1997
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| Keywords | cyclin-dependent protein kinase / protein phosphorylation / substrate specificity / enzyme inhibitor |
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| Research Abstract |
Cdc2 kinase or cdk5, a member of cyclin-dependent protein kinases, phosphorylates a Ser/Thr site immediately followed by a proline which acts as the substrate specificity determinant. We have examined structural features of proline which are essential for the substrate recognition by the kinase and found that the pyrrolidine ring of proline is primarily important. In addition, we observed that cdk5 has a stronger preference for a proline and basic residues on the carboxyl-terminal side of the phosphorylation site when compared to the preference exhibited by cdc2 kinase. These results gave useful information for developing spesific substrates and competitive inhibitors for each kinase. To obtain substrates/inhibitors which are resistant to enzymatic proteolysis, we undertook a synthesis of cyclic or retro-inverso peptides. Cyclic peptides which represent the site of histone or vimentin were effectively phosphorylated by cdc2 kinase. Thus, cyclization might be suitable for the purpose. We faced with some problems in the synthesis of retro-inverso peptides and are now testing conditions for obtaining objectives quantitatively.
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