2006 Fiscal Year Final Research Report Summary
Synthesis of Oxygen-Carrying Synthetic Hemoprotein Composed of Recombinant Albumin- Protoheme Complex
| Project/Area Number |
16350093
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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 | 一般 |
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| Research Field |
Chemistry related to living body
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| Research Institution | Waseda University |
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Principal Investigator |
KOMATSU Teruyuki Waseda University, Institute for Sci. & Eng., Associate Professor (30298187)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAGAWA Akito Waseda University, Institute for Sci. & Eng., Research Associate (20348858)
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| Project Period (FY) |
2004 – 2006
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| Keywords | Protein / Bioinorganic Chemistry / Biotechnology / Biomimetic Chemistry / Albumin-Protoheme / Recombinant Albumin / Synthetic Hemoprotein / Oxygen Adduct Complex |
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| Research Abstract |
The aim of this project is to develop oxygen-carrying synthetic hemoprotein by incorporation of iron-protoporhyrin IX(protoheme) into recombinant human serum albumin(rHSA) with proximal histidine coordination(rHSA-heme complex). The heme pocket structure which can control the oxygen-binding equilibrium of the heme would be elucidated.
In the first year, the rHSA was prepared by site-directed mutagenesis and the oxygen-binding ability of the rHSA-heme complex was analyzed. The molecular environment obviously affects the oxygen binding of the heme. In the second year, we succeeded to increase the oxygen-binding affinity by introduction of a distal base into the heme pocket Furthennore, the heme was exchanged with zinc-protoporphyrin IX(ZnPP) and the obtained rHSA-ZnPP could act as a photosensitizer of reduction of water to hydrogen. In the third year, we optimized the heme pocket structure and finally prepared the rHSA-heme complexes having identical oxygen-binding affinities with hemoglobin and red blood cells.
We clearly showed that the new methodology to confer the oxygen-binding capability to the simple plasma protein, HSA. These results were published as 17 original papers, 1 review and 2 chapters of the book. The entirely synthetic rHSA-heme complex could be of extreme medical importance for red blood cell substitute.
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Research Products
(87 results)
