On the Interaction between Thymidylic Acid and Sulfhydrylamine Radioprotectors

Abstract

The nature of the binding between certain sulfhydrylamine radioprotectors and diammonium deoxythymidylate (dTMP) was studied using ESR and x-ray diffraction techniques on solid systems prepared by freeze-drying and solution evaporation. ESR spectra taken after x-irradiation of an L-cysteine hydrochloride-dTMP system showed no spin transfer to the sulfur atom in contrast to the large amount of spin transfer exhibited by a cysteamine hydrochloride-dTMP system. X-Ray diffraction powder patterns of the two unirradiated solid systems showed that no unreacted material was present. Over 99% of the reaction between cysteamine hydrochloride and dTMP proceeded via binding through an enolate form of the thymine ring. In the case of L-cysteine hydrochloride, approximately 40% of the reaction involved binding of the radioprotector to the phosphate group. Indirect arguments lead to the conclusion that very little of this reaction takes place through the enolate group. These observations are consistent with the hypothes...