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反应体系pH对聚乙二醇牛血红蛋白偶联物性质的影响

常琛 尤国兴 王巍 李伟丹 王瑛 朱凯 周虹 赵莲 陈玉芝

军事医学2024,Vol.48Issue(10):753-759,7.
军事医学2024,Vol.48Issue(10):753-759,7.DOI:10.7644/j.issn.1674-9960.2024.10.005

反应体系pH对聚乙二醇牛血红蛋白偶联物性质的影响

Effect of pH value of reaction system on properties of pegylated bovine hemoglobin conjugate

常琛 1尤国兴 1王巍 2李伟丹 1王瑛 1朱凯 1周虹 1赵莲 1陈玉芝1

作者信息

  • 1. 军事科学院军事医学研究院,北京 100850
  • 2. 解放军总医院第四医学中心,北京 100089
  • 折叠

摘要

Abstract

Objective To explore the impact of pH value of the reaction system on the properties of bovine hemoglobin modified with aldehydeated polyethylene glycol(PEG-bHb).Methods PEG-bHb conjugates were synthesized under varying pH conditions(6.0,6.5,7.4 and 8.0)of the reaction system while consistent molar ratios,temperature,and reaction time were maintained.The structural and functional attributes of PEG-bHb were characterized.Results The proportion of methemoglobin decreased with an increase in pH.In a weakly acidic reaction environment,the PEG-bHb was found to be relatively highly modified.At pH 6.5,the average number of PEG chains attached to the bHb surface was 6.86±0.38.Selective PEG modification of the N-terminal α-NH2 groups was more pronounced under weakly acidic conditions.Specifically,at pH 6.5,the modification efficiency of the N-terminal α-NH2 groups of bHb by aldehyde-activated PEG reached 95.4%for the α-chains and 99.3%for the β-chains.The PEG modification influenced the heme region microenvi-ronment of bHb,with minimal structural impact observed at pH 6.5.After modification,the oxygen affinity of PEG-bHb was enhanced,the Hill coefficient was reduced,and there were significant increases in colloid osmotic pressure,viscosity,and particle size,all of which differed markedly from the unmodified bHb group(P<0.001).Conclusion The synthesis of PEG-bHb under weakly acidic conditions can result in a high degree of selective modification of the N-terminal α-NH2 groups and an overall high degree of modification.

关键词

红细胞代用品/聚乙二醇/牛血红蛋白/选择性修饰

Key words

red blood cell substitutes/polyethylene glycol/bovine hemoglobin/selective modification

分类

医药卫生

引用本文复制引用

常琛,尤国兴,王巍,李伟丹,王瑛,朱凯,周虹,赵莲,陈玉芝..反应体系pH对聚乙二醇牛血红蛋白偶联物性质的影响[J].军事医学,2024,48(10):753-759,7.

军事医学

OACSTPCD

1674-9960

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