High O2 affinity hemoglobin-based oxygen carriers synthesized via polymerization of hemoglobin with ring-opened 2-chloroethyl-β-D-fructopyranoside and 1-o-octyl-β-D-glucopyranoside
High O2 affinity hemoglobin-based oxygen carriers synthesized via polymerization of hemoglobin with ring-opened 2-chloroethyl-β-D-fructopyranoside and 1-o-octyl-β-D-glucopyranoside
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DOI：
10.1002/bit.21277
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发表时间：
2007-06-15
影响因子：
3.8
通讯作者：
Palmer, Andre F.
中科院分区：
文献类型：
--
作者：
Dimino, Michael L.;Palmer, Andre F.
正在开发具有高O-2亲和力（低P-50）的第二代基于血红蛋白的O-2载体（HBOC），以抑制由过度氧合组织引起的血管收缩，这是与低O-2亲和力第一代HBOC相关的问题。我们的小组先前已经研究了血红蛋白（Hb）与二醛的聚合作为工程高O-2亲和力HBOCs的策略。本研究通过2-氯乙基-β-D-吡喃果糖苷（2-CEFP）和1-邻辛基-β-D-吡喃葡萄糖苷（1-OGP）分别在1，2-二醇位上开环，合成了两种新的反应性二醛，得到了新的血红蛋白。聚合试剂。通过使R-状态牛血红蛋白（bHb）与开环的2-CEFP和1-OGP以范围从10：1至30：1的交联剂与bHb的摩尔比反应来合成高亲和力聚合的HBOC。所得聚合的牛HBOCs（bHBOCs）显示P（50）范围。从7到18毫米汞柱，协同性范围从0.8到1.4，高铁血红蛋白（metHb）水平范围从3%到10%。交联反应还稳定了bHbs与开环1-OGP以交联剂与bHb的摩尔比为20：1和30：1反应以及bHbs与开环2-CEFP以摩尔比为30：1反应的第三阶Adair系数。此外，每种聚合的bHBOC的数均分子量M-n大于bHb。通过增加交联剂与bHb的摩尔比，获得了倾向于较大分子量bHBOCs的分子量分布。总之，本研究的结果已经确定了新的Hb聚合试剂，易于合成，并且能够产生具有更高的O-2亲和力和重均分子量的bHBOCs相比，bHb。
Second generation hemoglobin-based O-2 carriers (HBOCs) are being developed with high O-2 affinity (low P-50) in order to suppress vasoconstriction elicited by over-oxygenating tissues, a problem associated with low O-2 affinity first generation HBOCs. Our group has previously investigated the polymerization of hemoglobin (Hb) with dialdehydes as a strategy for engineering high O-2 affinity HBOCs. In this study, two novel reactive dialdehydes were synthesized by ring-opening 2-chloroethyl-beta-D- fructopyranoside (2-CEFP) and 1-o-octyl-beta-D-glucopyranoside (1-OGP) at the 1,2-diol position, respectively, to yield novel Hb. polymerizing reagents. High-affinity polymerized HBOCs were synthesized by reacting R-state bovine hemoglobin (bHb) with ring-opened 2-CEFP and 1-OGP at crosslinker to bHb molar ratios ranging from 10:1 to 30:1. The resulting polymerized, bovine HBOCs (bHBOCs) displayed P(50)s ranging. from 7 to 18 mmHg, cooperativities ranging from 0.8 to 1.4, and methemoglobin (metHb) levels ranging from 3% to 10%. The cross-linking reaction also stabilized the, third stepwise Adair coefficient for bHbs reacted with ring-opened 1-OGP at cross-linker to bHb molar ratios of,20:1 and 30:1 and for bHbs reacted with ring-opened 2-CEFP at molar ratios of 30:1. Additionally, the number-averaged molecular weight, M-n, of each polymerized bHBOC was larger compared to bHb. Molecular weight distributions leaning towards larger molecular weight bHBOCs were obtained by increasing the cross-linker to bHb molar ratio. Taken together, the results of this study have identified novel Hb polymerization reagents that are easy to synthesize, and that are capable of yielding bHBOCs with higher O-2 affinities and weight-averaged molecular weights compared to bHb.