Specifically crosslinked hemoglobin with free functionality

C - Chemistry – Metallurgy – 07 – K

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C07K 14/805 (2006.01) A61K 47/48 (2006.01) C07C 69/86 (2006.01) C07K 1/113 (2006.01) A61K 38/00 (2006.01)

Patent

CA 2149132

2149132 9411399 PCTABS00032 Hemoglobin is site-specifically crosslinked into its tetrameric form by reaction with a trifunctional reagent which combines electrostatic effects, steric effects and the presence of functional groups so that two of the functional groups react with specific sites on the hemoglobin whilst the third site is left free for reaction with endogenous nucleophilic compounds. A specific example of such a crosslinking reagent is trimesoyl tris(3,5-dibromosalicylate), TTDS, which effects specific crosslinking between the amino groups of lysine-82 on each respective .beta. sub-unit. While the crosslinking reagent TTDS has three available carboxyl groups for the crosslinking reaction, only two so react, leaving one free carboxyl for reaction with exogenous nucleophiles, e.g. to render the hemoglobin product useful as a carrier for nucleophilic compounds through the body's circulatory system.

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