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A triply modified human adult hemoglobin with low oxygen affinity, rapid autoxidation and high tetramer stability | |
Yan, Wenying1,3; Shen, Lijuan1; Yu, Weili1; Wang, Ying2; Wang, Quan2; You, Guoxing2; Zhao, Lian2; Zhou, Hong2; Hu, Tao1 | |
2020-09-15 | |
Source Publication | INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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ISSN | 0141-8130 |
Volume | 159Pages:236-242 |
Abstract | 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. |
Keyword | Hemoglobin Oxygen Affinity, Autoxidation |
DOI | 10.1016/j.ijbiomac.2020.05.007 |
Language | 英语 |
WOS Keyword | Bovine Hemoglobin ; Functional-properties ; Pegylation ; Oxidation ; Substitutes ; Carriers ; Binding ; Alters ; Chains ; Heme |
Funding Project | National Natural Science Foundation of China[81700181] ; National Natural Science Foundation of China[31970875] ; National Natural Science Foundation of China[81703445] |
WOS Research Area | Biochemistry & Molecular Biology ; Chemistry ; Polymer Science |
WOS Subject | Biochemistry & Molecular Biology ; Chemistry, Applied ; Polymer Science |
Funding Organization | National Natural Science Foundation of China |
WOS ID | WOS:000564254900008 |
Publisher | ELSEVIER |
Citation statistics | |
Document Type | 期刊论文 |
Identifier | http://ir.ipe.ac.cn/handle/122111/41882 |
Collection | 中国科学院过程工程研究所 |
Corresponding Author | Zhao, Lian; Zhou, Hong; Hu, Tao |
Affiliation | 1.Chinese Acad Sci, State Key Lab Biochem Engn, Inst Proc Engn, Beijing 100190, Peoples R China 2.Acad Mil Med Sci, Inst Hlth Serv & Transfus Med, Beijing 100850, Peoples R China 3.Univ Chinese Acad Sci, Beijing 100190, Peoples R China |
Recommended Citation 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. |
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A triply modified hu(1013KB) | 期刊论文 | 出版稿 | 限制开放 | CC BY-NC-SA | Application Full Text |
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