Side-chain selective and covalent labelling of proteins with transition organometallic complexes. Perspectives in biology

Abstract

This article reviews the current methods available to covalently label peptides and proteins with transition organometallic entities in a side-chain-selective and covalent manner. Almost all these methods take advantage of the reactivity of the nucleophilic groups borne by most proteins, namely the e-amino function of lysine residues and the thiol function of cysteine residues. In this way, the unusual physical and/or spectroscopic properties of transition metals and their organo-complexes may be exploited in different areas of biology and medicine, including analytical biochemistry, protein three-dimensional structure analysis and radio-pharmaceuticals development. To cite this article: M.

Cysteine‐Specific, Covalent Anchoring of Transition Organometallic Complexes to the Protein Papain from Carica papaya

“…[22][23][24][25] During the past ten years, we have designed and prepared several families of transition organometallic complexes for the side-chain specific and covalent labelling of proteins, and studied their reactivity with, inter alia, bovine serum albumin (BSA), hen egg white lysozyme (HEWL) or avidin. [26,27] Most of these reagents targeted the protein primary amines borne by lysine residues and the N-terminal amino acid. However, as proteins generally carry a lot of these functions, labelling was not chemoselective but generally involved several binding sites, which yielded mixtures of modified proteins.…”

Intramolecular carbonyl⋯carbonyl interactions in W, Mo and Fe complexes containing the η1-N-maleimidato ligand: X-ray, DFT and AIM studies

“…Covalently labelled biomolecules with transition metal complexes are very interesting species because their unusual redox properties [10], IR absorption [11] or luminescence features [12][13][14] enable their sensitive detection in biological samples. The reaction rates of transition metal complexes containing the maleimidato ligand with thiol groups in biomolecules were already investigated.…”

Analysis of cysteine-containing proteins using precolumn derivatization with N-(2-ferroceneethyl)maleimide and liquid chromatography/electrochemistry/mass spectrometry

“…The solvents used for LC/MS were acetonitrile and water at LC/MS grade quality from Biosolve (Valkenswaard, The Netherlands). N-(2-Ferroceneethyl)maleimide (FEM) was synthesized from ferrocenylmethyltrimethylammonium iodide (obtained from Alfa Aesar, Karlsruhe, Germany) according to a method described in the literature [21,26,27] that was modified as indicated below.…”

“…It was originally developed by Shimada et al for the determination of thiols by HPLC with electrochemical detection [19,20]. Later it was also used to introduce an IR probe [21], a redox-active reporter group [22], and an electroactive label into a nonelectroactive enzyme [23] in order to design new electrochemical biosensors. Furthermore, the attachment of maleimide-containing ferrocene derivatives onto selfassembled alkanethiol and alkanedithiol monolayers was studied [24].…”