Structural Arrangement Functional Group Disposition of Artificial Peptide Hydroxamate Ligands by Complex Formation with Metal Ions
| Project/Area Number |
11650884
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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 |
Synthetic chemistry
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| Research Institution | TOKYO UNIVERSITY OF AGRICULTURE AND TECHNOLOGY |
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Principal Investigator |
AKIYAMA Masayasu TOKYO UNIVERSITY OF AGRICULTURE AND TECHNOLOGY, FACULTY OF TECHNOLOGY, PROFESSOR, 工学部, 教授 (20016728)
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| Co-Investigator(Kenkyū-buntansha) |
TSUBOUCHI Akira TOKYO UNIVERSITY OF AGRICULTURE AND TECHNOLOGY, FACULTY OF TECHNOLOGY, RESEARCH ASSISTANT, 工学部, 助手 (40272637)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2000: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1999: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | Hydroxamic Acid / Peptide / Complex / Functional Material / Histidine / Imidazole / Hydrolysis |
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| Research Abstract |
In the first place, several tripodal mono- and ditopic hydroxamate ligands were synthesized by combining three units of one of H-(Ala)n-β-(HO)Ala(n=1,2,3) and (Ala)n-β-(HO)Ala-Ala-β-(HO)Ala peptides, respectively, with nitrilotriacetic acid. These mono- and ditopic ligands form complexes with Fe(III) in well-defined manners. The resulting structures, kinetic behavior, and thermodynamic properties of the Fe(III) complexes depend on the number and the chiral nature of Ala residues in the chains, as evidenced by CD spectroscopy and Fe(III)-exchange reactions with EDTA.
Secondly, three His residues were incorporated in the tris(2-aminoethyl)amine-based peptide hydroxamates, to construct enzyme active site models. When combined with Fe(III), the functional histidine imidazole groups were arranged at suitable positions, thereby exhibiting catalytic activity for hydrolysis of carboxylic amides and esters. In particular, the three His residues in the Fe(III)-bound ligand provide a metal coordination site for Zn(II), providing a carbonic anhydrase (CA) active site model ; the hydrolysis of p-nitrophenyl acetate by the hydroxide-ion bound to Zn(II) was observed.
Thirdly, ribonuclease A-mimetic compounds carrying two His residues were synthesized as tripodal hydroxamate peptides extending from one Orn residue. After combining with Fe(III), the resulting complexes promote the hydrolysis of UpU (uridylyl-3', 5'-uridine) overwhelmingly compared to the corresponding concentration of free imidazole. A bell-shaped rate vs pH profile was obtained as a result of the acid and base catalysis of the two imidazole groups.
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Report
(3 results)
Research Products
(6 results)
