Agents that target cysteine residues of biomolecules and their therapeutic potential

Abstract

Modification of cysteine residues in proteins, due to (i) the participation of the thiol moiety of this amino acid in oxido-reductions reactions; (ii) its ability to strongly co-ordinate transition metal ions; or (iii) its nucleophilic nature and facile reaction with electrophiles, are of critical importance in the design of novel types of pharmacological agents. Application of such procedures recently led to the design of novel antivirals, mainly based on the reaction of zinc finger proteins with disulfides and related derivatives. This approach was particularly successful for developing novel anti-HIV and anti-HPV agents. Several new anticancer therapeutic approaches, mainly targeting tubulin, Ras and farnesyl transferase among others, have also been reported, as well as the design of gastric H⁺/K⁺-ATP-ase inhibitors as anti-ulcer drugs. Other miscellaneous agents/procedures based on cysteine modification reactions are also reviewed, but have fewer applications at present. In conclusion, this unique amino acid offers very interesting possibilities for the development of particularly useful pharmacological agents, which generally possess a completely different mechanism of action compared to classical agents in clinical use, thus avoiding major problems such as multi-drug resistance (for antivirals and chemotherapeutic agents) or high toxicity.

• anticancer agents
• antivirals
• cysteine
• disulfides
• dithiocarbamates
• farnesyl transferase inhibitor
• glutathione
• HIV
• +/+-ATP-ase inhibitors
• HPV
• pentafluorosulfonamides
• Ras
• S-glutathione-transferase
• sulfonamides
• thiols
• tubulin
• zinc fingers