| Modulation of expression and polymerization of hemoglobin Polytaur, a potential blood substitute. | |
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MedLine Citation:
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PMID: 20920461 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Chemically or genetically modified hemoglobins are a therapeutic class indicated for the treatment of a variety of hypo-oxygenation pathologies, severe trauma-related hemorrhages or elective surgery when blood transfusions are refused or not available. Recombinant heterologous hemoglobins offer the possibility of a potentially unlimited production and genetically optimized properties in terms of oxygen affinity, NO reactivity and resistance to autoxidation. Hemoglobin Polytaur is an autopolymerizing human-bovine hybrid mutant, previously obtained as a 500kDa polymer, shown to reduce the infarct volume from focal cerebral ischemia in in vivo animal models. In this work, hemoglobin Polytaur polymerization, carried out under conditions to minimize heme oxidation and modification, resulted in a 180kDa cyclic homogeneous trimer of hemoglobin tetramers. This novel oligomer was characterized by electrophoresis, MALDI-TOF mass spectrometry and gel filtration. The size and the oxygen binding properties were shown to be ideally suited for its use as a blood substitute. Co-expression with the human α hemoglobin-stabilizing protein (AHSP), a chaperone that assists hemoglobin folding in vivo, resulted in an unexpected decrease in yield and in unusual spectroscopic and functional properties, suggesting the formation of strong protein-protein interactions that reduce the expression, hinder the tetramer assembly and prevent purification. |
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Authors:
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Serena Faggiano; Stefano Bruno; Luca Ronda; Paolo Pizzonia; Barbara Pioselli; Andrea Mozzarelli |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Archives of biochemistry and biophysics Volume: 505 ISSN: 1096-0384 ISO Abbreviation: Arch. Biochem. Biophys. Publication Date: 2011 Jan |
Date Detail:
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Created Date: 2010-12-08 Completed Date: 2011-01-19 Revised Date: 2012-03-02 |
Medline Journal Info:
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Nlm Unique ID: 0372430 Medline TA: Arch Biochem Biophys Country: United States |
Other Details:
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Languages: eng Pagination: 42-7 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 Elsevier Inc. All rights reserved. |
Affiliation:
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Department of Biochemistry and Molecular Biology, University of Parma, Parma, Italy. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Blood Proteins / genetics Blood Substitutes / chemistry, metabolism* Cattle Gene Expression Hemoglobins / chemistry, genetics*, metabolism* Humans Molecular Chaperones / genetics Molecular Weight Oxygen / metabolism Protein Multimerization Recombinant Proteins / chemistry, genetics, metabolism |
| Chemical | |
Reg. No./Substance:
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0/AHSP protein, human; 0/Blood Proteins; 0/Blood Substitutes; 0/Hemoglobins; 0/Molecular Chaperones; 0/Recombinant Proteins; 7782-44-7/Oxygen |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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