Bis-pyridoxal polyphosphates: a new class of specific intramolecular crosslinking agents for hemoglobin.
A series of compounds related to bis-pyridoxal phosphate has been synthesized and used to crosslink deoxyhemoglobin. The yield of crosslinked hemoglobin increased dramatically from about 15% for the di- or triphosphate to about 70% for the tetraphosphate. The site of attachment of the intramolecular crossbridge was found to be from the N-terminal amino group of one beta chain to lysine 82 of the other. Since the distance between these residues is only 11A, the bis-pyridoxal tetraphosphates probably have a "stacked" conformation. The crosslinked hemoglobins bind oxygen cooperatively but with a greatly decreased affinity. The increased ability to unload oxygen together with the stabilization of the tetramer qualifies them as promising cell-free blood substitutes.
Benesch
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Department of Biochemistry and Molecular Biophysics, Columbia University, New York, N.Y. 10032.
Kwong
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D003432:Cross-Linking Reagents / Q000378:metabolism*; D006454:Hemoglobins / Q000378:metabolism*; D007202:Indicators and Reagents; D007700:Kinetics; D046911:Macromolecular Substances; D010108:Oxyhemoglobins / Q000378:metabolism; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives* / Q000378:metabolism; D013329:Structure-Activity Relationship
D003432:Cross-Linking Reagents; D006454:Hemoglobins; D007202:Indicators and Reagents; D046911:Macromolecular Substances; D010108:Oxyhemoglobins; D011732:Pyridoxal Phosphate