Biochemical basis of the interactions of heme with scavenger plasma proteins: analysis, quantification and approaches to intervention

• Applicant: Professorin Dr. Diana Imhof
• Subject Area: Biochemistry
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 545272732

The aim of this project proposal is to record the heme-scavenging capacity of the blood and to use this knowledge to develop molecules with heme-scavenging properties and to develop a method with which heme can be determined in the blood in the presence of hemoglobin and other interfering factors. The background for this is hemolytic reactions, which, after erythrocyte rupture, lead to a massive release of initially hemoglobin and, in turn, labile heme. However, the extent of (patho)physiological relevance of the interaction of labile heme with plasma proteins depends on the spatial and temporal hierarchy of simultaneous processes as well as the plasma levels and heme-binding affinities of heme-binding proteins within the intravascular compartment. From our studies, the binding of labile heme to hemoglobin and the heme scavenger hemopexin is known, but not that of the other potential scavenger plasma proteins. Accordingly, the proteins haptoglobin, human serum albumin, a1-microglobulin, a2-macroglobulin and a1-antitrypsin will be examined for their heme binding and possible heme transfer between hemoglobin and the potential heme scavenger. In order to estimate the total binding capacity of the blood, a matrix is used to classify all possible combinations of proteins. The variants are designed experimentally in such a way that the known, physiological plasma concentrations of the proteins are mapped, including taking into account concentration fluctuations in, for example, acute phase situations. From these studies at the peptide and protein level, artificial molecules will be derived that represent efficient heme scavengers. After evaluating their heme-binding capacity, these will be used to initiate studies to develop a diagnostic, non-instrumental-analytical method for heme determination that could be quickly used for field trials and point-of-care applications.

• DFG Programme: Research Grants