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Preliminary study of mechanism of action of SN38 derivatives. Physicochemical data, evidence of interaction and alkylation of DNA octamer d(GCGATCGC)2

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The synthesis of water‐soluble SN38 derivatives is presented, and their stability in solutions used during drug development studies has been investigated. A preliminary study of mechanism of action of 9‐aminomethyl… Click to show full abstract

The synthesis of water‐soluble SN38 derivatives is presented, and their stability in solutions used during drug development studies has been investigated. A preliminary study of mechanism of action of 9‐aminomethyl SN38 is presented. Using NMR techniques, the interaction of the oligomer d(GCGATCGC)2 is studied, showing that the terminal GC base pairs are the main site of interaction. Using pulsed field gradient spin echo and mass spectroscopy, evidence of a spontaneous alkylation reaction of the DNA oligomer with SN38 derivatives is presented. A proposed mechanism of reaction is suggested. Copyright © 2016 John Wiley & Sons, Ltd.

Keywords: sn38; preliminary study; study mechanism; mechanism action; sn38 derivatives

Journal Title: Magnetic Resonance in Chemistry
Year Published: 2017

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