Transition-Metal Complexes as Enzyme-Like Reagents for Protein Cleavage
type: CreativeWork
description: In this thesis, metal-promoted hydrolytic cleavage of the amide bond in histidine-containing dipeptides, has been studied. Transition-metal complexes are emerging as new reagents for selective cleavage of unactivated amide bonds in proteins. Such complexes bind to the side chains of methionine and histidine forming an inert complex with the N-terminal amino acid in the peptide. This binding is a prerequisite for subsequent cleavage, which occurs near these “anchoring” residues. We designed transition metal complexes for the cleavage of the first peptide bond downstream from the anchoring side chain of histidine. For this purpose, a series of ligands and their corresponding metal complexes, containing various divalent metal ions, such as Pd(II), Zn(II), Cu(II), Co(II), Ni(II) and Cd(II) have been synthesized. To complete their characterization, beside 1H and 13C NMR data, FAB/ESI-MS data and elemental analysis, crystallographic data of nine complexes have been obtained. They gave further insight into the geometry and nature of binding in synthesized metal complexes. In the course of this thesis, the role of the synthesized transition metal complexes as the promotores in the cleavage of the amide bond in small peptides, was examined. To supress the formation of hydrolytically inactive promoter-substrate complexes, the N-terminus of the dipeptides was protected by the acetylation. The histidine residue was placed either on the N- (AcHisGly) or C-terminus (AcbAlaHis) of the dipeptides. The rate of cleavage was monitored by following the 1H NMR resonances of free glycine. In addition, the possibilities to couple one of the new ligands with NTA (N-nitrilotriacetic acid) moiety, were investigated. In that compound, metal complex of the ligand could act as a peptidase, while the NTA moiety is known as an important and well characterized chelator for the oligo-histidine tag. It could be shown that, in this case, the carbodiimide method and mixed anhydride method are coupling…
abstract: In this thesis, metal-promoted hydrolytic cleavage of the amide bond in histidine-containing dipeptides, has been studied. Transition-metal complexes are emerging as new reagents for selective cleavage of unactivated amide bonds in proteins. Such complexes bind to the side chains of methionine and histidine forming an inert complex with the N-terminal amino acid in the peptide. This binding is a prerequisite for subsequent cleavage, which occurs near these “anchoring” residues. We designed transition metal complexes for the cleavage of the first peptide bond downstream from the anchoring side chain of histidine. For this purpose, a series of ligands and their corresponding metal complexes, containing various divalent metal ions, such as Pd(II), Zn(II), Cu(II), Co(II), Ni(II) and Cd(II) have been synthesized. To complete their characterization, beside 1H and 13C NMR data, FAB/ESI-MS data and elemental analysis, crystallographic data of nine complexes have been obtained. They gave further insight into the geometry and nature of binding in synthesized metal complexes. In the course of this thesis, the role of the synthesized transition metal complexes as the promotores in the cleavage of the amide bond in small peptides, was examined. To supress the formation of hydrolytically inactive promoter-substrate complexes, the N-terminus of the dipeptides was protected by the acetylation. The histidine residue was placed either on the N- (AcHisGly) or C-terminus (AcbAlaHis) of the dipeptides. The rate of cleavage was monitored by following the 1H NMR resonances of free glycine. In addition, the possibilities to couple one of the new ligands with NTA (N-nitrilotriacetic acid) moiety, were investigated. In that compound, metal complex of the ligand could act as a peptidase, while the NTA moiety is known as an important and well characterized chelator for the oligo-histidine tag. It could be shown that, in this case, the carbodiimide method and mixed anhydride method are coupling…
author: Pavlovic Rosman, Dina
date published: 2005-12-21
date modified: 2026-07-24T02:30:19Z
provider: Universität Heidelberg
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Universität Heidelberg