The reaction of the anticancer drug cisplatin with proteins most likely precedes the reaction with DNA in the body.  When reaction with DNA occurs, cell death is observed.  Due to the affinity of cisplatin for sulfur-containing amino acids, such as cysteine, reaction with proteins may occur prior to access to the DNA.  This is inconvenient for two reasons: first, if the drug reacts with an amino acid residue of a protein, the drug cannot reach the cancerous DNA to trigger cell death, and second, reaction with a sulfur-containing amino acid causes harmful side effects and is believed to be the cause of the drugs toxicity.  If reaction with non-sulfur-containing amino acids such as histidine could be favored, these side effects could be reduced and potentially eliminated.  Two platinum (II) oxalate compounds, using either ethylenediamine or tetramethylethylenediamine as the carrier ligand, have been synthesized for use in our experiments.  We believe that by adding bulk to the carrier ligand of the platinum compound (tetramethylethylenediamineplatinum(II) oxalate versus ethylenediamineplatinum(II) oxalate), the reaction rates with sulfur-containing amino acids could be slowed down enough that reaction with a non-sulfur-containing amino acid would be favored.  This would retain the success rate of the drugs in killing cancerous cells while possibly eliminating the side effects and toxicity caused.

Reaction rates of amino acids with derivatives of the anticancer drug cisplatin

248th National Meeting (2014)

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