Department of Chemistry , Nara Medical University , 840 Shijo-cho , Kashihara 634-8521 , Japan.
Biomacromolecules. 2019 Apr 8;20(4):1592-1602. doi: 10.1021/acs.biomac.8b01789. Epub 2019 Feb 15.
Hemoglobin (Hb), an oxygen-carrying protein, has an αβ tetrameric structure that dissociates reversibly into two αβ dimers (αβ ⇄ 2αβ). We synthesized a cyclic Hb-ring monomer with two β subunits bound through a 10 kDa polyethylene glycol (PEG) chain. The monomer induced ring-opening polymerization to produce a supramolecular polymer via intersubunit interaction of αβ dimers of an Hb molecule at the PEG terminals. Both the ring-closed monomer and the ring-opened supramolecular polymer were then fixed covalently by intramolecular cross-linking of two β subunits. Quantification of fixed products at various monomer concentrations revealed the equilibrium constant ( K), a ratio of propagation and depropagation rate constants, as 5.68 mM. The average degree of polymerization ([Formula: see text]) increased proportionally, concomitantly with the initial monomer concentration. Hb polymer with [Formula: see text] = 13.2 ( M = ca. 1 MDa) was obtained by cross-linking at 2.33 mM. Our novel strategy of ring-opening polymerization of Hb will eventually realize a highly aligned and efficiently polymerized Hb for creating artificial oxygen carriers for a clinical use.
血红蛋白（Hb）是一种携氧蛋白，具有αβ四聚体结构，可可逆地解离为两个αβ二聚体（αβ ⇄ 2αβ）。我们合成了一种环状 Hb 单体，其中两个β亚基通过 10 kDa 的聚乙二醇（PEG）链结合。单体诱导开环聚合，通过 PEG 末端 Hb 分子的αβ二聚体之间的亚基相互作用产生超分子聚合物。然后，通过两个β亚基的分子内交联将闭环单体和开环超分子聚合物固定为共价键。在各种单体浓度下固定产物的定量分析揭示了平衡常数（K），即增长和去增长速率常数的比值为 5.68 mM。聚合度（[Formula: see text]）与初始单体浓度成正比增加。通过在 2.33 mM 时交联，获得聚合度为 [Formula: see text] = 13.2 的 Hb 聚合物（M 约为 1 MDa）。我们的 Hb 开环聚合的新策略最终将实现高度排列和高效聚合的 Hb，用于制造用于临床应用的人工氧载体。
