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.
Department of Biochemistry & Molecular Biology and ‡Department of Chemistry, University of Chicago , 929 East 57th Street, Chicago, Illinois 60637, United States.|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.
Nan-Sheng
NS
Li
Department of Biochemistry & Molecular Biology and ‡Department of Chemistry, University of Chicago , 929 East 57th Street, Chicago, Illinois 60637, United States.|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.
Nathan P
NP
Gossai
Department of Biochemistry & Molecular Biology and ‡Department of Chemistry, University of Chicago , 929 East 57th Street, Chicago, Illinois 60637, United States.|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.
Jordan A
JA
Naumann
Department of Biochemistry & Molecular Biology and ‡Department of Chemistry, University of Chicago , 929 East 57th Street, Chicago, Illinois 60637, United States.|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.
Peter M
PM
Gordon
Department of Biochemistry & Molecular Biology and ‡Department of Chemistry, University of Chicago , 929 East 57th Street, Chicago, Illinois 60637, United States.|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.
Joseph A
JA
Piccirilli