Synthesis and characterization of a novel hemoglobin based blood substitute.

摘要

The development of a blood substitute has spanned more than a full century. Many various strategies have been developed that range from completely synthetic approaches to the use of modified hemoglobin. The results of these projects have suggested that in order to avoid the side-effects observed with previously developed blood substitutes the new model must have an increased molecular weight and contain antioxidant enzymes. As a result we have developed a hemoglobin-based blood substituted with increased molecular weight and presence of antioxidant enzymes. One unique aspect of this type of a compound is its utilization of the complementary chemistry between maleimides and sulfhydryls. To our knowledge this is the first attempt to utilize this type of chemistry for the purpose of hemoglobin polymerization. The analysis of this compound has shown that a hemoglobin polymer with molecular weight range from 64 kDa to >700 kDa has been created. Addition of antioxidant enzymes into the synthesis did not alter the molecular weight distribution. However, fractional analysis of the polymer showed that the antioxidant enzymes were primarily found in the heavier part of the polymer. In addition, oxidation rates of the entire polymer with antioxidant enzymes were smaller than those of a control. These results indicate that the polymerization method we have developed produced an ordered polymer formation and that enzyme function was not compromised during the process. In this dissertation, the focus will be on describing the process of the development and synthesis of this type of a polymer which has been specifically geared to be used as a blood substitute.