Intramolecularly cross-linked hemoglobin and method of preparation
AssigneeUniversity of Maryland
InventorsEnrico Bucci, Clara Fronticelli-Bucci, Ramachandra Hosmane
Life of this patent
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Abstract
Stroma-free hemoglobin cross-linked with reagents that mimic 2,3 diphosphoglycerate and transform stroma-free hemoglobin into a physiologically competent oxygen carrier which is retained in vivo for adequate periods of time and thus can be used in fluids for transporting oxygen; reagents for cross-linking stroma-free hemoglobin and method for cross-linking stroma-free hemoglobin.
Claims42
Cross-linked stroma-free hemoglobin obtained by cross-linking stroma-free hemoglobin with at least one cross-linking reagent selected from the group consisting of compounds of the general formulae (I) and (II):
- ##STR16## wherein one of R.sub.1 or R.sub.2 represents an electron-withdrawing atom or group, and the other of R.sub.1 or R.sub.2 represents a leaving atom or group or an electron-withdrawing group containing a leaving atom or group;
- one of R.sub.3 or R.sub.4 represents an electron-withdrawing atom or group, and the other of R.sub.3 or R.sub.4 represents a leaving atom or group or an electron-withdrawing group containing a leaving atom or group;
- R.sub.5 and R.sub.10, which may be the same or different, each represents an electron-withdrawing atom or group or an electron-withdrawing group containing a leaving atom or group;
- one of R.sub.6 or R.sub.7 represents a hydrogen atom, an alkyl group, an aryl group, or a heterocyclic group, and the other of R.sub.6 or R.sub.7 represents a leaving atom or group;
- one of R.sub.8 or R.sub.9 represents a hydrogen atom, an alkyl group, an aryl group or a heterocylic group, and the other of R.sub.8 or R.sub.9 represents a leaving atom or group;
- X represents a linking atom or group, n=0 to 4, m=0 to 4 and l=0 to 4.
A method of producing cross-linked stroma-free hemoglobin, comprising:
- (a) cross-linking stroma-free hemoglobin with at least one cross-linking reagent selected from the group consisting of compounds of the general formulae (I) and (II):
- ##STR17## wherein one of R.sub.1 or R.sub.2 represents an electron-withdrawing atom or group, and the other of R.sub.1 or R.sub.2 represents a leaving atom or group or an electron-withdrawing group containing a leaving atom or group;
- one of R.sub.3 or R.sub.4 represents an electron-withdrawing atom or group, and the other of R.sub.3 or R.sub.4 represents a leaving atom or group or an electron-withdrawing group containing a leaving atom or group;
- R.sub.5 and R.sub.10, which may be the same or different, each represents an electron-withdrawing atom or group or an electron-withdrawing group containing a leaving atom or group;
- one of R.sub.6 or R.sub.7 represents a hydrogen atom, an alkyl group, an aryl group, or a heterocyclic group, and the other of R.sub.6 or R.sub.7 represents a leaving atom or group;
- one of R.sub.8 or R.sub.9 represents a hydrogen atom, an alkyl group, an aryl group or a heterocyclic group, and the other of R.sub.8 or R.sub.9 represents a leaving atom or group;
- X represents a linking atom or group, n=0 to 4, m=0 to 4 and l=0 to 4;
- and
- (b) purifying the resulting cross-linked hemoglobin.
Dependencies are inferred from the claim text.