| Non-conservative surface decoration of hemoglobin: influence of neutralization of positive charges at PEGylation sites on molecular and functional properties of PEGylated hemoglobin. | |
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MedLine Citation:
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PMID: 18452721 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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High hydrodynamic volume, high viscosity and high colloidal osmotic pressure (COP) of PEGylated hemoglobin (Hb) have been suggested to neutralize the vasoactivity of acellular Hb. Consequences of non-conservative PEGylation (positive charge of the amino groups at the PEGylation sites is neutralized) using succinimidyl-ester of propionic acid PEG5K on the properties of PEGylated Hb have now been investigated. Non-conservative PEGylation of Hb leads to a much higher increase in the COP and viscosity of Hb than conservative extension arm facilitated (EAF) PEGylation of Hb. Introduction of alphaalpha-fumaryl crosslinking decreased the COP of non-conservative PEGylated Hb by stabilization of interdimeric interactions. Compared to the EAF-PEGylated alphaalpha-fumaryl Hb, non-conservative PEGylated product shows a comparable COP and higher viscosity. Conservative PEGylation of alphaalpha-fumaryl Hb by reductive alkylation chemistry does not increase the COP to this level, but enhanced the molecular volume and viscosity comparable to EAF-PEGylated product. Thus, the molecular properties of PEGylated Hb can be fine tuned using different PEGylation platforms and provide a unique opportunity for the design of second generation PEGylated Hbs. |
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Authors:
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Dongxia Li; Tao Hu; Belur N Manjula; Seetharama A Acharya |
Publication Detail:
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Type: Journal Article Date: 2008-04-11 |
Journal Detail:
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Title: Biochimica et biophysica acta Volume: 1784 ISSN: 0006-3002 ISO Abbreviation: Biochim. Biophys. Acta Publication Date: 2008 Oct |
Date Detail:
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Created Date: 2008-09-23 Completed Date: 2008-12-31 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0217513 Medline TA: Biochim Biophys Acta Country: Netherlands |
Other Details:
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Languages: eng Pagination: 1395-401 Citation Subset: IM |
Affiliation:
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Department of Physiology and Biophysics, Albert Einstein College of Medicine, Bronx, New York 10461, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Binding Sites Chromatography, High Pressure Liquid Circular Dichroism Colloids Hemoglobin A / chemistry, therapeutic use* Hemoglobins / chemistry*, therapeutic use Humans Peptide Mapping Polyethylene Glycols / chemistry*, metabolism, therapeutic use Protein Denaturation Surface Properties Viscosity |
| Chemical | |
Reg. No./Substance:
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0/Colloids; 0/Hemoglobins; 0/Polyethylene Glycols; 9034-51-9/Hemoglobin A |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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