Targeting Cysteine Residues of Biomolecules: New Approaches for the Design of Antiviral and Anticancer Drugs

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Abstract:

Modification of cysteine (Cys) 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 coordinate transition metal ions or (iii) its nucleophilic nature and facile reaction with electrophiles, may be of critical importance for 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 fanesyl transferase among others, have also been reported. Miscellaneous other agents / procedures which found less applications for the moment, and which are based on Cys modification reactions, are reviewed. This unique amino acid offers very interesting possibilities to develop particularly useful pharmacological agents, which generally possess a completely different mechanism of action as compared to classical agents in clinical use, avoiding their major problems such as multidrug-resistance of antivirals or antitumor agents or high toxicity associated with classical such chemotherapeutic agents.

Keywords: anti-hpv; antiviral anticancer; farneryl transferase; zinc finger protein

Document Type: Review Article

DOI: http://dx.doi.org/10.2174/0929867023370077

Publication date: June 1, 2002

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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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