Reversible protection of Cys-93(beta) by PEG alters the structural and functional properties of the PEGylated hemoglobin
文献类型:期刊论文
作者 | Wang, Qingqing1,2; Sun, Lijing1; Ji, Shaoyang1; Zhao, Dawei1,2; Liu, Jiaxin3; Su, Zhiguo1,4; Hu, Tao1 |
刊名 | BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
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出版日期 | 2014-07-01 |
卷号 | 1844期号:7页码:1201-1207 |
关键词 | PEGylation Hemoglobin Autoxidation Tetramer stability |
ISSN号 | 1570-9639 |
其他题名 | BBA-Proteins Proteomics |
中文摘要 | As a potential hemoglobin (Hb)-based oxygen carrier (HBOC), the PEGylated Hb has received much attention for its non-nephrotoxicity. However, PEGylation can adversely alter the structural and functional properties of Hb. The site of PEGylation is an important factor to determine the structure and function of the PEGylated Hb. Thus, protection of some sensitive residues of Hb from PEGylation is of great significance to develop the PEGylated Hb as HBOC. Here, Cys-93 (beta) of Hb was conjugated with 20 kDa polyethylene glycol (PEG20K) through hydrazone and disulfide bonds. Then, the conjugate was modified with PEG5K succinimidyl carbonate (PEG5K-SC) using acylation chemistry, followed by removal of PEG20K Hb with hydrazone hydrolysis and disulfide reduction. Reversible conjugation of PEG20K at Cys-93(beta) can protect Lys-95(beta), Val-1(alpha) and Lys-16(alpha) of Hb from PEGylation with PEG5K-SC. The autoxidation rate, oxygen affinity, structural perturbation and tetramer instability of the PEGylated Hb were significantly decreased upon protection with PEG20K. The present study is expected to improve the efficacy of the PEGylated Hb as an oxygen therapeutic. (C) 2014 Elsevier B.V. All rights reserved. |
英文摘要 | As a potential hemoglobin (Hb)-based oxygen carrier (HBOC), the PEGylated Hb has received much attention for its non-nephrotoxicity. However, PEGylation can adversely alter the structural and functional properties of Hb. The site of PEGylation is an important factor to determine the structure and function of the PEGylated Hb. Thus, protection of some sensitive residues of Hb from PEGylation is of great significance to develop the PEGylated Hb as HBOC. Here, Cys-93 (beta) of Hb was conjugated with 20 kDa polyethylene glycol (PEG20K) through hydrazone and disulfide bonds. Then, the conjugate was modified with PEG5K succinimidyl carbonate (PEG5K-SC) using acylation chemistry, followed by removal of PEG20K Hb with hydrazone hydrolysis and disulfide reduction. Reversible conjugation of PEG20K at Cys-93(beta) can protect Lys-95(beta), Val-1(alpha) and Lys-16(alpha) of Hb from PEGylation with PEG5K-SC. The autoxidation rate, oxygen affinity, structural perturbation and tetramer instability of the PEGylated Hb were significantly decreased upon protection with PEG20K. The present study is expected to improve the efficacy of the PEGylated Hb as an oxygen therapeutic. (C) 2014 Elsevier B.V. All rights reserved. |
WOS标题词 | Science & Technology ; Life Sciences & Biomedicine |
类目[WOS] | Biochemistry & Molecular Biology ; Biophysics |
研究领域[WOS] | Biochemistry & Molecular Biology ; Biophysics |
关键词[WOS] | RESONANCE RAMAN-SPECTRA ; UV CIRCULAR-DICHROISM ; POLYETHYLENE-GLYCOL ; OXYGEN CARRIERS ; TRYPTOPHAN RESIDUES ; MONO-PEGYLATION ; IN-VITRO ; MP4 ; CONJUGATION ; HB |
收录类别 | SCI |
原文出处 | |
语种 | 英语 |
WOS记录号 | WOS:000337211100004 |
公开日期 | 2014-08-28 |
版本 | 出版稿 |
源URL | [http://ir.ipe.ac.cn/handle/122111/10982] ![]() |
专题 | 过程工程研究所_研究所(批量导入) |
作者单位 | 1.Chinese Acad Sci, Inst Proc Engn, Natl Key Lab Biochem Engn, Beijing 100190, Peoples R China 2.Chinese Acad Sci, Grad Univ, Beijing 100049, Peoples R China 3.Chinese Acad Med Sci, Inst Blood Transfus, Chengdu 610052, Sichuan Provinc, Peoples R China 4.Collaborat Innovat Ctr Chem Sci & Engn, Tianjin, Peoples R China |
推荐引用方式 GB/T 7714 | Wang, Qingqing,Sun, Lijing,Ji, Shaoyang,et al. Reversible protection of Cys-93(beta) by PEG alters the structural and functional properties of the PEGylated hemoglobin[J]. BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS,2014,1844(7):1201-1207. |
APA | Wang, Qingqing.,Sun, Lijing.,Ji, Shaoyang.,Zhao, Dawei.,Liu, Jiaxin.,...&Hu, Tao.(2014).Reversible protection of Cys-93(beta) by PEG alters the structural and functional properties of the PEGylated hemoglobin.BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS,1844(7),1201-1207. |
MLA | Wang, Qingqing,et al."Reversible protection of Cys-93(beta) by PEG alters the structural and functional properties of the PEGylated hemoglobin".BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS 1844.7(2014):1201-1207. |
入库方式: OAI收割
来源:过程工程研究所
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