A triply modified human adult hemoglobin with low oxygen affinity, rapid autoxidation and high tetramer stability
文献类型:期刊论文
作者 | Yan, Wenying2,3; Shen, Lijuan2; Yu, Weili2; Wang, Ying1; Wang, Quan1; You, Guoxing1; Zhao, Lian1; Zhou, Hong1; Hu, Tao2 |
刊名 | INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES |
出版日期 | 2020-09-15 |
卷号 | 159页码:236-242 |
ISSN号 | 0141-8130 |
关键词 | Hemoglobin Oxygen Affinity, Autoxidation |
DOI | 10.1016/j.ijbiomac.2020.05.007 |
英文摘要 | The hypoxic environment of tumor may retard the efficacy of tumor therapeutic agents. Hemoglobin (Hb)-based oxygen carriers (HBOCs) could overcome the hypoxia of tumor by the oxygen delivery. However, typical HBOCs may not provide sufficient oxygen for their low oxygen transferring efficiency (OTE). In order to increase the OTE, human adult Hb (HbA) was subjected to triple modifications, i.e., alpha alpha-fumaryl crosslink at Lys-99(alpha), carboxymethylation at Val-1(alpha) and 8-arm PEG-based polymerization. Crosslink at Lys-99(alpha) and carboxymethylation at Val-1(alpha) synergistically led to a T-like quaternary structure of HbA. The dual modification significantly increased the partial oxygen pressure at 50% saturation (P50) of HbA from 14.8 mmHg to 34.6 mmHg and OTE from 9.1% to 33.1%. Eight-arm PEG-based polymerization slightly decreased the P50 of the Hb derivative to 27.8 mmHg and OTE to 30.5%. However, it can enlarge the molecular size of HbA and then prolong the serum duration of HbA. The triple modifications synergistically increased the autoxidation rate of Hb, which promote the production of reactive oxygen species (ROS). Therefore, the sufficient oxygen delivery and substantial pro-duction of ROS by the triply modified Hb may provide a potential strategy for tumor therapy. (C) 2020 Elsevier B.V. All rights reserved. |
WOS关键词 | Bovine Hemoglobin ; Functional-properties ; Pegylation ; Oxidation ; Substitutes ; Carriers ; Binding ; Alters ; Chains ; Heme |
资助项目 | National Natural Science Foundation of China[81700181] ; National Natural Science Foundation of China[31970875] ; National Natural Science Foundation of China[81703445] |
WOS研究方向 | Biochemistry & Molecular Biology ; Chemistry ; Polymer Science |
语种 | 英语 |
出版者 | ELSEVIER |
WOS记录号 | WOS:000564254900008 |
资助机构 | National Natural Science Foundation of China |
源URL | [http://ir.ipe.ac.cn/handle/122111/41881] |
专题 | 中国科学院过程工程研究所 |
通讯作者 | Zhao, Lian; Zhou, Hong; Hu, Tao |
作者单位 | 1.Acad Mil Med Sci, Inst Hlth Serv & Transfus Med, Beijing 100850, Peoples R China 2.Chinese Acad Sci, State Key Lab Biochem Engn, Inst Proc Engn, Beijing 100190, Peoples R China 3.Univ Chinese Acad Sci, Beijing 100190, Peoples R China |
推荐引用方式 GB/T 7714 | Yan, Wenying,Shen, Lijuan,Yu, Weili,et al. A triply modified human adult hemoglobin with low oxygen affinity, rapid autoxidation and high tetramer stability[J]. INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES,2020,159:236-242. |
APA | Yan, Wenying.,Shen, Lijuan.,Yu, Weili.,Wang, Ying.,Wang, Quan.,...&Hu, Tao.(2020).A triply modified human adult hemoglobin with low oxygen affinity, rapid autoxidation and high tetramer stability.INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES,159,236-242. |
MLA | Yan, Wenying,et al."A triply modified human adult hemoglobin with low oxygen affinity, rapid autoxidation and high tetramer stability".INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES 159(2020):236-242. |
入库方式: OAI收割
来源:过程工程研究所
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