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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 PublicationINTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
ISSN0141-8130
Volume159Pages: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.

KeywordHemoglobin Oxygen Affinity, Autoxidation
DOI10.1016/j.ijbiomac.2020.05.007
Language英语
WOS KeywordBovine Hemoglobin ; Functional-properties ; Pegylation ; Oxidation ; Substitutes ; Carriers ; Binding ; Alters ; Chains ; Heme
Funding ProjectNational Natural Science Foundation of China[81700181] ; National Natural Science Foundation of China[31970875] ; National Natural Science Foundation of China[81703445]
WOS Research AreaBiochemistry & Molecular Biology ; Chemistry ; Polymer Science
WOS SubjectBiochemistry & Molecular Biology ; Chemistry, Applied ; Polymer Science
Funding OrganizationNational Natural Science Foundation of China
WOS IDWOS:000564254900008
PublisherELSEVIER
Citation statistics
Document Type期刊论文
Identifierhttp://ir.ipe.ac.cn/handle/122111/41882
Collection中国科学院过程工程研究所
Corresponding AuthorZhao, Lian; Zhou, Hong; Hu, Tao
Affiliation1.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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