2019 Fiscal Year Final Research Report
Synthesis and in vivo characterization of polymer-multilinked hemoglobin assembly as artificial oxygen carrier
| Project/Area Number |
17K01367
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Biomedical engineering/Biomaterial science and engineering
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| Research Institution | Nara Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
酒井 宏水 奈良県立医科大学, 医学部, 教授 (70318830)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Keywords | 人工臓器学 / 血液代替物 / 高分子科学 / 超分子化学 / ヘモグロビン / 解離平衡 / 架橋 |
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| Outline of Final Research Achievements |
Various chemical modifications of hemoglobin (Hb) have been investigated to produce artificial oxygen carriers for use as red blood cells (RBC) substitutes. An Hb molecule has a stable α2β2 tetrameric structure which dissociates reversibly into two αβ dimers. In this work, we developed an efficient procedure to produce polymer-multilinked Hb assembly (PML-Hbs). We first synthesized a cyclic Hb monomer whose two β subunits were connected through a polyethylene glycol (PEG) chain. During the inter-molecular exchange of αβ subunits, the cyclic Hb monomer proceeded supramolecular ring-opening polymerization to produce a linear PML-Hbs. Hb units in the PML-Hbs were subsequently fixed covalently by site-specific cross-linking between two β subunits. The fixed PML-Hbs is a promising material for use as a RBC substitute, because it has a quite large molecular size (molecular weight of ca. 1,000,000) to prevent the extravasation, with showing reversible oxygen binding.
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| Free Research Field |
生体医工学・生体材料学
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| Academic Significance and Societal Importance of the Research Achievements |
Hbを重合することで人工酸素運搬体を作製する試みは過去に多数の報告があり、特に欧米において、ヒトへの投与を目指し研究が進められている。しかし、ランダム重合Hbは重合度が小さい上に分子量分布が広く、低分子量の成分が血管壁を透過して発現する副作用が問題となる。
本研究のように修飾Hbを単量体とみなして超分子重合する方法により得られるPML-Hbsは、決まった長さの高分子によりHb同士が連結されているためHbを規則的に配置でき、重合度の調節も可能であるなど、従来法に比べ多くの長所を有する。本研究で得られた知見は、既存のランダム重合法の副作用の問題を解決する糸口になると期待される。
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