In chemical and biological systems, iron is both ubiquitous and highly reactive. In a variety of circumstances, there is great need for new approaches to the removal of iron or the control of its reactivity. We have produced a series of high molecular weight iron chelators based on derivatization of a number of substrates with deferoxamine B. This chelator has an extremely high affinity for iron and is very selective (i.e., has relatively low affinity for other polyvalent cations aside from aluminum). We have produced adducts between deferoxamine B and both soluble polymers and solid matrices. The present proposal relates to maximization of derivatization procedures, definition of appropriate conditions of modification, and, finally, determination of the physical characteristics of the derivatized materials. The high molecular weight iron chelators produced as a result of this work have a number of potential (i.e., Phase II) applications. These include: (1) the selective and quantitative removal of iron from solutions, (2) a simple and rapid procedure for serum iron determination, (3) more effective iron chelation therapy, and (4) the control of bacterial infections which are promoted by free iron.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Small Business Innovation Research Grants (SBIR) - Phase II (R44)
Project #
5R44DK037207-03
Application #
3507326
Study Section
Biochemistry Study Section (BIO)
Project Start
1987-09-30
Project End
1990-08-31
Budget Start
1988-09-01
Budget End
1990-08-31
Support Year
3
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Biomedical Frontiers, Inc.
Department
Type
DUNS #
City
Minneapolis
State
MN
Country
United States
Zip Code
55414
Hedlund, B E; Hallaway, P E (1991) Role of iron and oxygen radicals in hemorrhage and shock. Klin Wochenschr 69:1113-7
Hedlund, B E; Hallaway, P E; Mahoney, J R (1990) High molecular weight forms of deferoxamine: novel therapeutic agents for treatment of iron-mediated tissue injury. Adv Exp Med Biol 264:229-34
Lesnefsky, E J; Hedlund, B E; Hallaway, P E et al. (1990) High-dose iron-chelator therapy during reperfusion with deferoxamine-hydroxyethyl starch conjugate fails to reduce canine infarct size. J Cardiovasc Pharmacol 16:523-8
Mahoney Jr, J R; Hallaway, P E; Hedlund, B E et al. (1989) Acute iron poisoning. Rescue with macromolecular chelators. J Clin Invest 84:1362-6