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

Nan-Sheng Li; Nathan P Gossai; Jordan A Naumann; Peter M Gordon; Joseph A Piccirilli

doi:10.1021/acs.bioconjchem.6b00557

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

Bioconjug Chem. 2016 Oct 19;27(10):2575-2579. doi: 10.1021/acs.bioconjchem.6b00557. Epub 2016 Oct 6.

Authors

Nan-Sheng Li^{1

2}, Nathan P Gossai^{1

2}, Jordan A Naumann^{1

2}, Peter M Gordon^{1

2}, Joseph A Piccirilli^{1

2}

Affiliations

¹ Department of Biochemistry & Molecular Biology and ‡Department of Chemistry, University of Chicago , 929 East 57th Street, Chicago, Illinois 60637, United States.
² Department of Pediatrics, Division of Pediatric Hematology and Oncology and ∥Masonic Cancer Center, University of Minnesota , MMC 366, 420 Delaware Street SE, Minneapolis, Minnesota 55455, United States.

PMID: 27690393
DOI: 10.1021/acs.bioconjchem.6b00557

Abstract

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.