Modified hemoglobin molecules and uses thereof

Abstract

Compositions that include a globin, such as hemoglobin, in a relaxed state are described. Globin molecules in a relaxed state (R state) have a higher binding affinity for carbon monoxide and oxygen than globin molecules in a tense state (T state). Hemoglobin in a relaxed state can be, for example, hemoglobin that is substantially free of 2,3-diphosphoglycerate or hemoglobin that includes a beta-Cys93 that is covalently modified to inhibit one or both salt bridges between beta-Asp94, beta-His146 and alpha-Lys40. Methods for using these compositions, such as for treating carbon monoxide poisoning, and methods for producing these compositions, are also disclosed.

Description

[0001] Cross References to Related Applications [0002] This application claims the benefit of U.S. Provisional Application No. 62 / 828,269, filed April 2, 2019, which is hereby incorporated by reference in its entirety. [0003] Statement of Government Support [0004] This invention was made with government support under Grant Numbers HL098032, HL007563, HL110849, HL103455, HL136857, and HL125886 awarded by the National Institutes of Health. The government has certain rights in this invention. technical field [0005] The present disclosure relates to compositions comprising globin in a relaxed state, such as hemoglobin free of 2,3-diphosphoglycerate and / or hemoglobin comprising a covalently modified β-Cys93 residue. The present disclosure also relates to methods of treating carboxyhemoglobinemia and methods for making hemoglobin comprising modified β-Cys93 residues. Background technique [0006] Exposure to carbon monoxide through inhalation is a major cause of envi...

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However, this therapy has only a limited effect on CO clearance, is not available on site due to the complexit...

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