Document Detail


Oxidized mono-, di-, tri-, and polysaccharides as potential hemoglobin cross-linking reagents for the synthesis of high oxygen affinity artificial blood substitutes.
MedLine Citation:
PMID:  15176904     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Various oxidized mono/di/tri/poly saccharides were studied as potential hemoglobin (Hb) cross-linkers in order to produce oxygen carriers with high oxygen affinities (low P(50)'s) and high molecular weights (therefore lower macromolecular diffusivities compared to tetrameric Hb). Such physical properties were desired to produce polymerized hemoglobins (PolyHbs) with oxygen release profiles similar to that of human blood, as was demonstrated in work by Winslow (1). In this present study, bovine hemoglobin was cross-linked with a variety of oxidized (ring-opened) saccharides, which resulted in cross-linked Hb species ranging in size from 64 to 6400 kDa (depending on the particular oxidized saccharide used in the reaction) and P(50)'s ranging from 6 to 15 mmHg. A parallel synthetic approach was used to synthesize these carbohydrate-hemoglobin conjugates, and asymmetric flow field-flow fractionation (AFFF) coupled with multi-angle static light scattering (MASLS) was used to measure the absolute molecular weight distribution of these PolyHb dispersions. Cross-linking reactions were conducted at two pHs (6 and 8), with larger cross-linked Hb species produced at pH 8 (where hydrolysis was most likely to occur between glycosidic bonds linking adjacent saccharide rings) rather than at pH 6. The largest molecular weight species formed from these reactions consisted of Hb cross-linked with ring-opened lactose, maltose, methylglucopyranoside, sucrose, trehalose, and 15 kDa and 71 kDa dextran at high pH (pH 8). The most promising Hb cross-linker was methylglucopyranoside, which resulted in very large cross-linked Hb species, with low P(50)'s and lower methemoglobin (metHb) levels compared to the other Hb cross-linking reagents.
Authors:
Julie H Eike; Andre F Palmer
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Publication Detail:
Type:  Comparative Study; Evaluation Studies; Journal Article    
Journal Detail:
Title:  Biotechnology progress     Volume:  20     ISSN:  8756-7938     ISO Abbreviation:  Biotechnol. Prog.     Publication Date:    2004 May-Jun
Date Detail:
Created Date:  2004-06-04     Completed Date:  2004-12-15     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8506292     Medline TA:  Biotechnol Prog     Country:  United States    
Other Details:
Languages:  eng     Pagination:  953-62     Citation Subset:  IM    
Affiliation:
Department of Chemical and Biomolecular Engineering, University of Notre Dame, Notre Dame, Indiana 46556, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Biocompatible Materials / analysis,  chemistry
Blood Substitutes / analysis,  chemical synthesis,  chemistry*
Cattle
Cross-Linking Reagents / chemistry*
Feasibility Studies
Hemoglobins / analysis,  chemistry*
Hydrogen-Ion Concentration
Materials Testing
Molecular Weight
Multiprotein Complexes / analysis,  chemistry
Oxidation-Reduction
Oxygen / chemistry*
Polymers / chemistry
Polysaccharides / chemistry*
Protein Binding
Protein Conformation
Chemical
Reg. No./Substance:
0/Biocompatible Materials; 0/Blood Substitutes; 0/Cross-Linking Reagents; 0/Hemoglobins; 0/Multiprotein Complexes; 0/Polymers; 0/Polysaccharides; 7782-44-7/Oxygen

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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