Phenols and Polyphenols as Antioxidants and Anticancer Agents
In order to replicate, a mammalian cell must replicate its genetic material which involves the synthesis of DNA. The reductive conversion of ribonucleotides to deoxynucleotides, catalyzed by the enzyme ribonucleotide reductase, is a rate limiting step in the DNA biosynthetic pathway (1). The endogenous pools of deoxynucleotides are not sufficient to support de novo DNA synthesis. Therefore, this key step in DNA synthesis represents a prime target for the development of an anticancer compound. Mammalian ribonucleotide reductase consists of two non-identical protein subunits. The larger subunit acts as a regulatory subunit since it contains the allosteric effectors (nucleotides) binding domains. The small subunits contain a pair of ferric ions and are able to generate a tyrosyl free radical which play a vital role in the reductive reaction (2). The reducing equivalents is supplied by either of two small molecular weight sulfhydryl proteins thioredoxin or glutaredoxin (1).
KeywordsHydroxamic Acid Ribonucleotide Reductase Allosteric Effector Inhibit Ribonucleotide Reductase Exhibit Antitumor Activity
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