2000 Fiscal Year Final Research Report Summary
Design and Functional Evaluation of Albumin Mutants for Improving Medicinal Efficacy
| Project/Area Number |
10557245
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| Research Category |
Grant-in-Aid for Scientific Research (B).
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
応用薬理学・医療系薬学
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| Research Institution | KUMAMOTO UNIVERSITY |
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Principal Investigator |
OTAGIRI Masaki Fac.Pharm.Sci., KUMAMOTO UNIVERSITY Prof., 薬学部, 教授 (80120145)
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| Co-Investigator(Kenkyū-buntansha) |
KUWATA Shigeki Chemo-Sera-Ther.Res.Inst., Head Res., 主任研究員
IMAI Teruko Fac.Pharm.Sci., KUMAMOTO UNIVERSITY Guest Prof., 薬学部, 客員教授 (70176478)
TANASE Sumio Sch.Med.Sci., KUMAMOTO UNIVERSITY Assoc.Prof., 医学部, 助教授 (20112401)
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| Project Period (FY) |
1998 – 2000
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| Keywords | Albumin preparation / Site-directed mutagenesis / Molecular design / Artificial blood / Functional evaluation / Blood preparation |
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| Research Abstract |
This investigation was undertaken to develop a safe and effective albumin using site-directed mutagenesis techniques. The results obtained in this study are as follow :
1) Two single-mutants (K199A, K525A) were produced. The recombinant albumins were correctly folded, as evidenced by the fact that they showed similar patterns as the native albumin in the far- and near-UV CD spectrum as well as reactivity towards polyclonal anti-serum raised against native albumin.
2) Thermal denaturation experiments by using GdnCl and DSC revealed no significant difference in conformational stability for native and mutant albumins.
3) The ligand binding properties and esterase-like activity of the albumin mutants were nearly the same as those for the native albumin.
4) The plasma levels of the albumin mutants labeled with ^<125>I after intravenous bolus injections to rats showed two-phase profiles but their half-lives were shorten than that for the native albumin.
From the above results, there are potentials for the design of such albumin mutants but further investigations need to be carried out in order to serve the objectives of better safety and efficacy of albumin preparation.
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Research Products
(18 results)
