ABSTRACT
In this chapter we have compared the structural models developed for the bindings of the breast antitumor drugs tamoxifen, 4-hydroxytamoxifen, and endoxifen with DNA and tRNA. Multiple spectroscopic methods and molecular modeling were used to characterize the drug binding sites, binding constant, and the effect of drug binding on DNA and tRNA stability and conformation. Structural analysis showed that tamoxifen and its metabolites bind DNA and tRNA via hydrophobic and hydrophilic interactions with tRNA forming more stable drug adducts than DNA and 4-hydroxytamoxifen forms stronger conjugate with polynucleotides. The negative free binding energy showed that drug complexation is spontaneous at room temperature.
