Efficient Synthetic Approach to Linear Dasatinib-DNA Conjugates by Click Chemistry

A pair of synthetic approaches to linear dasatinib-DNA conjugates via click chemistry are described. The first approach involves the reaction of excess azido dasatinib derivative with 5′-(5-hexynyl)-tagged DNAs, and the second involves the reaction of excess alkynyl-linked dasatinib with 5′-azido-tagged DNA. The second approach using alkynyl-derived dasatinib and 5′-azido-tagged DNA yielded the corresponding dasatinib-DNA conjugates in higher yield (47% versus 10-33% for the first approach). Studies have shown these linear dasatinib-DNA conjugates-derived gold nanoparticles exhibit efficacy against leukemia cancer cells with reduced toxicity toward normal cells compared to that of free dasatinib.