Cysteine metal complexes

Fodran, P., Moravcikova, R, Kolek, E. and Brezovd, V. 2008. Transformation of substituted cinnamic acids using L-cysteine metal complexes in aqueous media. Food Res. Int. 41 429-132. 

The sulfur atom is a favorable zinc ligand because of its size and polarizability. The thiol side chain of cysteine (p/Cg —8.5) is negatively charged as it complexes a metal ion in a protein in addition to metal coordination, the cysteine thiol may simultaneously accept hydrogen bonds from other protein residues (Adman et al, 1975 Ippolito et al, 1990). Hydrogen bond networks with cysteine metal ligands are discussed further in Section I11,B. 

The LFMM FF for the oxidized Cu(II) centers was designed around suitable homoleptic species, viz., [Cu(imidazole)4]2+, [Cu(SCH3)4]2-, [Cu(S(CH3)2)4]2+, and [Cu(0=CH2)4]2+ (37). These complexes represent models for Cu-histidine, Cu-cysteine, Cu-methionine, and Cu-glutamine O/peptide respectively. Only the first of these species is known experimentally. However, it is amply documented that DFT gives excellent structures for metal complexes (64,65) so we can access the remaining species computationally (Fig. 20). 

Cyclopentene-l-dithiocarboxylic acid, 2-amino-mctal complexes, 800 Cyclophosphazenes metal complexes, 81 Cyclotetraphosphazene, octamethyl-platinum complexes, 82 Cyclotetraphosphazenes metal complexes, 81 Cyclotriphosphorus complexes, 1058 Cysteine... 

Hopkins and co-workers [6] have used the selective complexation of transition metals by two distant EDTA modified amino acids to stabilize the a-helical conformation of peptides 2 and 3 (Fig. 3). The results were particularly impressive in the case of 3 where the helicity increased from 0 to about 80% upon complexation of Cd2 4 ions. Along the same lines, Ghadiri and coworkers [7] reported the important stabilization of the helical conformation of 4 and 5 by the formation of selective metal complexes (Ru2+, Zn2+, Cu2+, and Cd2+) involving either two imidazoles of histidines or one imidazole and one thiol from a cysteine separated by three amino acids (I, 1 + 4) (Fig. 4). They also reported that peptide 4 is Cd2+-selective and that the helical conformation of the inert Ru2+ complex of 5 is remarkably stable. For instance, it has a melting point 25 °C higher than the uncomplexed peptide in water. 

Fig. 4. Illustration of an a-helical peptide stabilized by a transition metal complex involving two histidine or one histidine and one cysteine side chains. (Reprodnced with the permission of Ref. 7)...

The metal ion-promoted hydrolysis of a number of bidentate esters such as methyl 2,3-diaminopropionate (8), methyl histidinate (9), methyl cysteinate (10) and the ethyl ester of ethylenediaminemonoacetate (11) have been studied. The first three esters give very thermodynamically stable metal complexes in solution with pendant ester functions.64"71 Typical kinetic data for these systems are given in Tables 9 and 10. 

Cat B is an abundant and ubiquitously expressed cysteine peptidase of the papain family and makes up a major fraction of lysosomal enzymes that is capable of degrading components of the extracellular matrix in various diseases [30-32]. Cat B is also a prognostic marker for several types of cancer [33], and increased expression and secretion of cat B has been shown to be involved in the migration and invasion of various tumours [34—36], The precise role of cat B in solid tumours is not fully understood, but it has been proposed to participate, along with other cysteine cathepsins, in metastasis, angiogenesis, and tumour progression [37], Indeed, cat B inhibitors reduce both tumour cell motility and invasiveness in vitro [38], Recently, metal complexes based on rhenium, gold and palladium were shown to be effective inhibitors of cat B [39-44],... 

Functionalisation of the complexes with reactive groups a number of metal complexes have been modified with (1) an NHS ester, isothiocyanate, and aldehyde, which can react readily with amines of lysine and the A-terminal of proteins and (2) iodoacetamide and maleimide that can react with sulfhydryls of the cysteine residue [3-5, 10]. These facile reactions lead to covalent attachment of luminescent complexes to the target proteins and amine-/sulfhydryl-modified oligonucleotides. 

As a first step toward this purpose, we have studied the chelation effect of tetrapeptides of sequences Cys-X-Y-Cys, by preparation of metal complexes of mainly the first transition series. The hydrophobic effect of the peptides was also studied by utilizing the side chain bulkiness of the amino acid residues interposed between the two cysteine residues. A special effect of aromatic side chains of tyrosine, phenylalanine, and tryptophan has also been examined in order to assess their ability to ease electron transfer to and from the nearby iron core. 

Figure 7 Letkeman (1996) used chemical speciation calculations to estimate the major complexes for lead and mercury as a function of pH in a fluid having overall plasma composition. The results show that most metal complexes with low-molecular-weight organic ligands such as amino acids diminish in importance with decreasing pH (such as in the gastric fluids) due to the increased protonation of the organic ligands. Cl—chloride Cy—cysteinate Ct—citrate Glut— glutathione (reproduced by permission of the Division of Chemical Education Inc. from J. Chem. Educat.

Doornbos DA. Stabihty constants of metal complexes of L-cysteine, D-penicillamine, N-acetyl-D-peniciUamine and some biguanides. Determination of stoichiometric stabihty constants by an accurate method for pH measurement. Pharm Weekbl 1968 103(45) 1213-27. 

Solid-Supported Surface Catalysis by Metal Complexes. Hong et al. (1987a, b, in press) have prepared a variety of hybrid catalysts between Co(II) phthalocyanine complexes and the surfaces of silica gel, polystyrene-divinylben-zene, and Ti02 and tested these hybrids for catalytic activity with respect to the autoxidation of hydrogen sulfide, sulfur dioxide, 2-mercaptoethanol, cysteine, and hydrazine ... 

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