Hb Chemical Modifications and Nanoparticle Production

The Program Project seeks to determine the mechanisms responsible for the toxicities associated with acellular hemoglobins in blood and to establish biochemical and physiological strategies to prevent limit and/or reverse these adverse events. Core B is responsible for the chemical modification of wild type and mutant hemoglobins to manipulate their structure and function as required by the individual units of the Program Project. This Core will get mutant Hbs from the Project 2/Core C These mutants and wild type HbA will be chemically modified to modulate oxygen affinity and nitrite reductase activity (NR activity), cross-linked to prevent dissociation, PEGylated to increase the molecular size, viscosity and colloid osmotic pressure (COP), and oligomerized to enhance the molecular size and effective Hb concentration. This Core will coordinate with the rest of the units of the Program Project to decide the molecular characteristics of the hemoglobin products required for the studies of individual units and develop strategies to design these products. The Core will also be responsible for the preparation of nanoparticles designed in Project 3 and manipulate the preparation protocols to customize the release patterns of the enclosed components. The functions of the Core B are: 1. Synthesize PEGylated/chemically modified wild type and mutant Hbs with the specifications required by the individual units of the program at 1 to 10 g levels. 2. Determine the molecular properties of the products including O2 affinity, viscosity, colloidal oncotic pressure (COP), and molecular size. 3. Standardize the preparation of nanoparticles designed in Project 3; customize the release profiles of the enclosed components, and prepare large amounts of nanoparticles for project 1 and core D.