Hemoglobin derivative co-conjugated with fatty acid-linked PEG and alkoxy PEG as a blood substitute
AssigneeSunBio Inc.
InventorsKwang Nho, Minjung Ahn, Changmin Hyun, JungHun Lee
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Abstract
The invention relates to hemoglobin derivative, particularly hemoglobin which is co-conjugated with both fatty acid-linked polyethylene glycol (FA-PEG) derivatives and alkoxy polyethylene glycol (alkoxy-PEG) derivatives, and a method for making such hemoglobin derivative. Various embodiments of the invention include crosslinked hemoglobin which is co-conjugated with both FA-PEG derivatives and alkoxy-PEG derivatives. Such hemoglobin derivative according to the invention exhibit non-toxicity and extended intravascular retention time.
Claims13
A hemoglobin derivative in which hemoglobin (Hb) or crosslinked hemoglobin (xHb) is covalently conjugated with a fatty acid-PEG (FA-PEG) derivative and an alkoxy-PEG derivative,
- wherein the Hb or xHb comprise one or more lysine residues, and an N-terminal valine residue,
- wherein the fatty-acid PEG derivative and the alkoxy-PEG derivative are each independently covalently conjugated to one of the lysine residues, or the N-terminal valine residues of the hemoglobin (Hb) or the crosslinked hemoglobin (xHb),
- wherein if the FA-PEG is covalently conjugated to the N-terminal valine residue of the Hb or xHb, then the alkoxy-PEG derivative is conjugated to one or more of the lysine residues of the Hb or xHb,
- wherein if the alkoxy-PEG is covalently conjugated to the N-terminal valine residue of the Hb or xHb, then the FA-PEG derivative is conjugated to one or more of the lysine residues of the Hb or xHb,
- wherein the crosslinked hemoglobin (xHb) is crosslinked between any two subunits of hemoglobin via bis(3,5-dibromosalicyl)fumarate or bis(3,5-dibromosalicyl)succinate,
- wherein the crosslinked hemoglobin (xHb) is intra-molecularly crosslinked between two alpha subunits or two beta subunits of hemoglobin via bis(3,5-dibromosalicyl)fumarate or bis(3,5-dibromosalicyl)succinate.
Dependencies are inferred from the claim text.