Synthesis and Evaluation of Amyloid beta Derived and Amyloid beta Independent Enhancers of the Peroxidase-like Activity of Heme

摘要

Labile heme has been suggested to have 'an impact in, several severe diseases. In the context of Alzheimer's disease,(AD) however, decreased levels of free heme have been reported. Therefore, we were looking for an assay system that can be used for heme concentration determination. From a biochemical point of view the peroxidase-activity of the A beta-heme complex seemed quite attractive to pursue this pal. As a consequence, a peptide that is able to increase the readout even in the case of a low heme concentration is favorable. The examination,of A beta- and non A beta-derived peptides in complex with herrie revealed that the peroxidase-like activity significantly depends on the, peptide sequence and length. A 23mer His based peptide derived from human fatty acyl-CoA reductage 1 in complex with heme 'exhibited a significantly higher peroxidase activity than A beta(40)-heme. Structural 'modeling of both complexes demongtrated that binding via a histidine can be supported by hydrogen bond interactions of a basic residue near-the propionate carboxyl function of protoporphyrin IX. Furthermore, the interplay of A beta-heme and the lipoprotein LDL as a potential Physiological effector of A beta was examined.