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JOURNAL ARTICLE
RESEARCH SUPPORT, NON-U.S. GOV'T
A Stepwise Approach for the Synthesis of Folic Acid Conjugates with Protein Kinase Inhibitors.
Journal of Organic Chemistry 2017 December 16
Herein, we report an alternative synthetic approach for selected 2,6,9-trisubstituted purine CDK inhibitor conjugates with folic acid as a drug-delivery system targeting folate receptors. In contrast to the previously reported approaches, the desired conjugates were constructed stepwise using solid-phase synthesis starting from immobilized primary amines. The ability of the prepared conjugates to release the free drug was verified using dithiothreitol (DTT) and glutathione (GSH) as liberating agents. Finally, binding to the folate receptor (FOLR1) overexpressed in a cancer cell line was measured by flow cytometry using a fluorescent imaging probe.
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