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Reversible protection of Cys-93(beta) by PEG alters the structural and functional properties of the PEGylated hemoglobin
Alternative TitleBBA-Proteins Proteomics
Wang, Qingqing1,2; Sun, Lijing1; Ji, Shaoyang1; Zhao, Dawei1,2; Liu, Jiaxin3; Su, Zhiguo1,4; Hu, Tao1
2014-07-01
Source PublicationBIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
ISSN1570-9639
Volume1844Issue:7Pages:1201-1207
AbstractAs 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.; 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.
KeywordPegylation Hemoglobin Autoxidation Tetramer Stability
SubtypeArticle
WOS HeadingsScience & Technology ; Life Sciences & Biomedicine
DOI10.1016/j.bbapap.2014.04.005
URL查看原文
Indexed BySCI
Language英语
WOS KeywordRESONANCE RAMAN-SPECTRA ; UV CIRCULAR-DICHROISM ; POLYETHYLENE-GLYCOL ; OXYGEN CARRIERS ; TRYPTOPHAN RESIDUES ; MONO-PEGYLATION ; IN-VITRO ; MP4 ; CONJUGATION ; HB
WOS Research AreaBiochemistry & Molecular Biology ; Biophysics
WOS SubjectBiochemistry & Molecular Biology ; Biophysics
WOS IDWOS:000337211100004
Citation statistics
Cited Times:7[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Version出版稿
Identifierhttp://ir.ipe.ac.cn/handle/122111/10982
Collection研究所(批量导入)
Affiliation1.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
Recommended Citation
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.
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