Low oxygen affinity mutant hemoglobins

A non-naturally occurring low oxygen affinity mutant hemoglobin with increased stability against autoxidation that has oxygen binding properties comparable to those of human normal adult hemoglobin in the presence of the allosteric effector 2,3-bisphosphoglycerate, wherein the asparagine residue at position 108 of each of the β-chains is replaced by a glutamine residue (SEQ ID NO:

• 8).

A non-naturally occurring mutant human hemoglobin wherein the asparagine residue at position 108 of the β-chains is replaced by a glutamine residue (SEQ ID NO:

• 8) wherein said hemoglobin possesses oxygen-binding properties of oxygen affinity as measured by P50 and cooperativity as measured by the Hill coefficient (nmax) and similar to those of Hb A in the presence of the allosteric effector 2,3-bisphosphoglycerate as follows:
• P50 about 17.4 mm Hg, nmax about 3.1 in 0.1 M sodium phosphate at pH 7.4 and 29° C.

An artificial mutant hemoglobin which in a cell-free enviornment has oxygen binding properties comparable to those of human normal adult hemoglobin in red blood cells wherein said hemoglobin contains a mutation such that the asparagine residue at position 108 of the β-chains is glutamine (SEQ ID NO:

• 8).

rHb (βN108Q) (SEQ ID NO:

• 8).

rHb (βN108Q) (SEQ ID NO:

• 8) derived from cells transformed with pHE7009.

A non-toxic pharmaceutical composition comprising a non-naturally occurring mutant hemoglobin wherein the asparagine residue at position 108 of the β-chains is replaced by a glutamine residue (SEQ ID NO:

• 8) in a pharmaceutically acceptable carrier.

A method of treating a human subject, comprising administering to said subject a nontoxic composition comprising an artificial mutant hemoglobin, wherein said artificial mutant hemoglobin is rHb (βN108Q) (SEQ ID NO:

• 8).