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  • Title: Targeted dendrimeric anticancer prodrug: a methotrexate-folic acid-poly(amidoamine) conjugate and a novel, rapid, "one pot" synthetic approach.
    Author: Zhang Y, Thomas TP, Desai A, Zong H, Leroueil PR, Majoros IJ, Baker JR.
    Journal: Bioconjug Chem; 2010 Mar 17; 21(3):489-95. PubMed ID: 20128612.
    Abstract:
    A targeted dendrimeric anticancer prodrug, a conjugate of generation 5 (G5) polyamidoamine (PAMAM) dendrimer, folic acid (FA), and methotrexate (MTX), has been successfully synthesized by using a novel "one pot" approach which is simple, reproducible, and feasible for large-scale synthesis. All dendrimer products have been characterized by (1)H NMR, MALDI-TOF, GPC, and HPLC. With this new method, the ratio of FA versus MTX attached to the dendrimer can be easily tuned to achieve the desired therapeutic effect. A new analytical approach for calculating the numbers of FA and MTX attached to the dendrimer has been established. In vitro studies performed on FA receptor-expressing KB cells show that the new conjugate has a similar affinity and cytotoxic potency to G5-FA-MTX synthesized using the traditional multiple-step approach.
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