Production and use of multimeric hemoglobins
AssigneeSomatogen, Inc.
InventorsDavid C. Anderson, Antony J. Mathews, Gary L. Stetler
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Abstract
Multimeric hemoglobin-like proteins are obtained by crosslinking cysteines of the component tetramers, or by genetically fusing globin-like domains of one tetramer with those of another, by means of an interdomain spacer sequence. Artificial cysteines are introduced selectively in a single globin-like domain per tetramer to control polymerization.
Claims74
A non-naturally occuring pseudotetrameric hemoglobin-like protein which is a pseudotetramer comprising four globin-like domains, said pseudotetramer comprising a pseudodimeric polypeptide having two substantially homologous globin-like domains, one of which is mutated to provide an asymmetric crosslinkable cysteine residue, the corresponding residue in the other globin-like domain of said pseudodimeric polypeptide being an amino acid other than cysteine, said pseudotetramer further comprising at least one other globin-like domain-bearing polypeptide.
A non-naturally occuring pseudooligomeric polypeptide comprising four or more globin-like domains.
A non-naturally occuring octameric hemoglobin-like protein which comprises two tetramers, each tetramer comprising two human alpha globin-like domains and two human beta globin-like domains, a cysteine in one tetramer being disulfide bonded to a corresponding cysteine in the second tetramer, the crosslinking of a third tetramer being essentially sterically prevented, with the proviso that the crosslinked cysteine is not at beta 83 (Hemoglobin Ta Li).
A non-naturally occuring pseudodimeric globin-like polypeptide having two substantially homologous globin-like domains, one of which is mutated to provide an asymmetric crosslinkable cysteine residue, the corresponding residue in the other globin-like domain of said pseudodimeric polypeptide being an amino acid other than cysteine.
Dependencies are inferred from the claim text.