24948-53-6Relevant academic research and scientific papers
Highly Cytotoxic Bioconjugated Gold(I) Complexes with Cysteine-Containing Dipeptides
Gutiérrez, Alejandro,Marzo, Isabel,Cativiela, Carlos,Laguna, Antonio,Gimeno, M. Concepci?n
, p. 11088 - 11095 (2015/11/10)
Several gold(I) complexes with cysteine-containing dipeptides have been prepared starting from cystine by coupling different amino acids and using several orthogonal protections. The first step is the reaction of cystine, where the sulfur centre is protected as disulfide, with Boc2O in order to protect the amino group, followed by coupling of an amino acid ester; finally the disulfide bridge is broken with mercaptoethanol to afford the dipeptide derivative. Further reaction with [AuCl(PPh3)] gives the gold-dipeptide-phosphine species. Starting from these formally gold(I) thiolate-dipeptide phosphine complexes with the general formula [Au(SR)(PR3)] different structural modifications, such as change in the type of the amino protecting group, the type of phosphine, the number of gold(I) atoms per molecule, or the use of a non-proteinogenic conformationally restricted amino acid ester, were introduced in order to evaluate their influence in the biological activity of the final complexes. The cytotoxic activity, in vitro, of these complexes was evaluated against different tumour human cell lines (A549, MiaPaca2 and Jurkat). The complexes show an outstanding cytotoxic activity with IC50 values in the very low micromolar range. Structure-activity relationship studies from the complexes open the possibility of designing more potent and promising gold(I) anticancer agents. Striking with gold: Gold(I) complexes with cysteine-containing dipeptides were prepared starting from cystine by coupling different amino acids, and using several orthogonal protections. The complexes show excellent cytotoxic activity with IC50 values in the very low micromolar range. The structural changes in the parent compound led to the synthesis of the most effective compound in the cell lines tested, which is the complex with two AuPPh3+ fragments coordinated to the Boc-Cys-Gly-OMe peptide (see scheme).
Cysteinyl peptide inhibitors of Bacillus cereus zinc β-lactamase
Bounaga, Sakina,Galleni, Moreno,Laws, Andrew P,Page, Michael I
, p. 503 - 510 (2007/10/03)
Several cysteinyl peptides have been synthesised and shown to be reversible competitive inhibitors of the Bacillus cereus metallo-β-lactamase. The pH dependence of pKi indicates that the thiol anion displaces hydroxide ion from the active site zinc(II). D,D-Peptides bind to the enzyme better than other diastereoisomers, which is compatible with the predicted stereochemistry of the active site.
Synthesis of Peptides Containing S-(N-Alkylcarbamoyl)cysteine Residues, Metabolites of N-Alkylformamides in Rodents and in Humans
Threadgill, Michael D.,Gledhill, Adrian P.
, p. 2940 - 2949 (2007/10/02)
Hydrochloride salts of S-(N-methylcarbamoyl), S-(N-ethylcarbamoyl), and S-(N,N-dimethylcarbamoyl) derivatives of cysteine, N-acetylcysteine, and cysteinylglycine have been prepared.S-(N-Methylcarbamoyl)glutathione hydrochloride has also been synthesized.Protecting groups for amino and carboxylic acid functions were selected for their ability to solubilize the peptides in dichloromethane in which solvent the thiols were treated with alkyl isocyanates and with N,N-dimethylcarbamoyl chloride.Removal of S-(amidomethyl) protecting groups using mercury(II) acetate was found to cause some loss of N-(tert-butoxycarbonyl) groups.Elimination of disulfide was evident during coupling of disulfide derivatives of cysteine using mixed anhydride methods but not with a carbodiimide coupling agent.Mixed disulfide protections were reductively cleaved by propane-1,3-dithiol.Many of the deprotected S-carbamoyl amino acids and peptides are metabolites of the corresponding N-alkylformamides in rodents and in humans.
