title: Synthesis and Evaluation of Amyloid β Derived and Amyloid β Independent Enhancers of the Peroxidase-like Activity of Heme.
abstract: 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 Aβ-heme complex seemed quite attractive to pursue this goal. 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 Aβ- and non-Aβ-derived peptides in complex with heme 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 reductase 1 in complex with heme exhibited a significantly higher peroxidase activity than Aβ(40)-heme. Structural modeling of both complexes demonstrated that heme 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 Aβ-heme and the lipoprotein LDL as a potential physiological effector of Aβ was examined.
authors.affiliation: Pharmaceutical Chemistry I, Pharmaceutical Institute, University of Bonn , Brühler Strasse 7, 53119 Bonn, Germany.
authors.forename: Amelie
authors.initials: A
authors.lastname: Wißbrock
authors.affiliation: Pharmaceutical Chemistry I, Pharmaceutical Institute, University of Bonn , Brühler Strasse 7, 53119 Bonn, Germany.
authors.forename: Toni
authors.initials: T
authors.lastname: Kühl
authors.affiliation: Pharmaceutical Chemistry I, Pharmaceutical Institute, University of Bonn , Brühler Strasse 7, 53119 Bonn, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Silbermann
authors.affiliation: Institute of Neuropathology, University Hospital Bonn , Sigmund Freud Strasse 25, 53105 Bonn, Germany.
authors.forename: Albert J
authors.initials: AJ
authors.lastname: Becker
authors.affiliation: Leibniz Institute on Aging-Fritz Lipmann Institute , Beutenbergstrasse 11, 07745 Jena, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Ohlenschläger
authors.affiliation: Pharmaceutical Chemistry I, Pharmaceutical Institute, University of Bonn , Brühler Strasse 7, 53119 Bonn, Germany.
authors.forename: Diana
authors.identifier: 0000-0003-4163-7334
authors.initials: D
authors.lastname: Imhof
mesh_terms: D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000502:physiology*; D001665:Binding Sites; D002384:Catalysis; D006418:Heme / Q000378:metabolism*; D006639:Histidine / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000378:metabolism; D008958:Models, Molecular; D010544:Peroxidases / Q000737:chemistry / Q000378:metabolism*; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D016229:Amyloid beta-Peptides; D008077:Lipoproteins, LDL; D006418:Heme; D006639:Histidine; D010544:Peroxidases