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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
1996-3-8
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pubmed:abstractText |
In previous studies mono-3,5-dibromosalicyl-fumarate was used to introduce an intramolecular crosslink (pseudo-crosslink) in the beta cleft between hemoglobin beta subunits. Sedimentation velocity analysis indicated that the product had a mean molecular weight indicating a tetramer with low dissociability. The product had a P50 higher than that of native hemoglobin and a plasma retention time in the rat of about 3 h, i.e., four times longer than untreated hemoglobin. However, the product contained a fraction which was rapidly eliminated in the urine and which had a short plasma half-time of about 20 min, indicating the presence of a dissociable fraction. We have attempted to further enhance the tetrameric stability of hemoglobin and prevent urine elimination by positioning a longer chain carboxylic acid than fumaric acid into the beta cleft. We reason that a longer molecule would allow for greater stabilizing interactions across the beta cleft. In the present study human and bovine hemoglobins were reacted with mono-3-5-dibromosalicyl muconate. Muconic acid is two carbons longer than fumaric acid. The products were acylated at the beta 82 (human) and beta 81 (bovine) lysines of the beta-cleft and had a low degree of dissociability. For reasons not presently understood, urine excretion was high and plasma half-time was not increased above that of untreated hemoglobin. In conclusion, it appears that only covalently crosslinked hemoglobins which are completely nondissociable tetramers escape filtration; tetramers with any degree of dissociability into dimers are filterable.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0003-9861
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
326
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
119-25
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:8579359-Amino Acid Sequence,
pubmed-meshheading:8579359-Animals,
pubmed-meshheading:8579359-Cattle,
pubmed-meshheading:8579359-Cross-Linking Reagents,
pubmed-meshheading:8579359-Hemoglobins,
pubmed-meshheading:8579359-Humans,
pubmed-meshheading:8579359-Molecular Sequence Data,
pubmed-meshheading:8579359-Protein Conformation,
pubmed-meshheading:8579359-Rats,
pubmed-meshheading:8579359-Sorbic Acid
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pubmed:year |
1996
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pubmed:articleTitle |
Stabilization of the tetrameric structure of human and bovine hemoglobins by pseudocrosslinking with muconic acid.
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pubmed:affiliation |
Department of Biochemistry, School of Medicine, University of Maryland at Baltimore 21201, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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