Low oxygen affinity mutant hemoglobin
AssigneeCarnegie Mellon University
InventorsChien Ho, Hyun-Won Kim, Tong-Jian Shen
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Abstract
A non-naturally occurring mutant hemoglobin (.alpha.96Val.fwdarw.Trp) is provided that has a lower oxygen affinity than that of native hemoglobin, but high cooperativity in oxygen binding. The mutant hemoglobin is preferably obtained by recombinant DNA techniques. Such a mutant hemoglobin may be used as a component of a blood substitute.
Claims15
A non-naturally occurring mutant human hemoglobin wherein the valine residue at position 96 of the .alpha. chain (SEQ ID NO:
- 1) is replaced by a tryptophan residue.
r Hb (.alpha.96Val.fwdarw.Trp) (SEQ ID NO:
- 1).
An artificial mutant human hemoglobin which in a cell-free environment has oxygen binding properties comparable to those of human normal adult hemoglobin in red blood cells wherein said hemoglobin contains a mutation of the valine residue at position 96 of the .alpha. chain (SEQ ID NO:
- 1).
The hemoglobin of claim 23 wherein said valine residue is replaced by a tryptophan residue.
A non-naturally occurring low oxygen affinity mutant hemoglobin that has oxygen binding properties comparable to those of human normal adult hemoglobin in the presence of the allosteric effector 2,3-diphosphoglycerate, wherein the valine residue at position 96 of the .alpha. chain is replaced by a tryptophan residue (SEQ ID NO:
- 1).
A non-naturally occurring mutant hemoglobin wherein said hemoglobin contains a mutation of the valine residue at position 96 of the .alpha. chain (SEQ ID NO:
- 1) possessing oxygen-binding properties of oxygen affinity as measured by P.sub.50 and cooperativity as measured by the Hill coefficient (n.sub.max) similar to those of Hb a in the presence of the allosteric effector 2,3-diphosphoglycerate as follows:
- P.sub.50 about 26.6, n.sub.max about 2.4 at pH 6.5;
- P.sub.50 about 22.0, n.sub.max about 2.5 at pH 6.8;
- P.sub.50 about 11.6, n.sub.max about 2.6 at pH 7.4;
- P.sub.50 about 5.6, n.sub.max about 2. 4 at pH 8.0.
r Hb (.alpha.96Val.fwdarw.Trp) (SEQ ID NO:
- 1) derived from cells transformed with plasmid pHE202.
r Hb (.alpha.96Val.fwdarw.Trp) (SEQ ID NO:
- 1) derived form cells transformed with plasmid pHE702.
A non-toxic pharmaceutical composition comprising a non-naturally occurring mutant hemoglobin wherein the valine residue at position 96 of the .alpha. chain is replaced by a tryptophan residue (SEO ID NO:
- 1) in a pharmaceutically acceptable carrier.
The composition of claim 19 wherein said hemoglobin is r Hb (.alpha.96Val.fwdarw.Trp) (SEO ID NO:
- 1).
Dependencies are inferred from the claim text.