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

Naumczuk Beata | Zendy; Kawęcki Robert | Zendy; Bocian Wojciech | Zendy; Bednarek Elżbieta | Zendy; Sitkowski Jerzy | Zendy; Kozerski Lech | Zendy

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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

Author(s) -

Naumczuk Beata,

Kawęcki Robert,

Bocian Wojciech,

Bednarek Elżbieta,

Sitkowski Jerzy,

Kozerski Lech

Publication year - 2017

Publication title -

magnetic resonance in chemistry

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 0.483

H-Index - 72

eISSN - 1097-458X

pISSN - 0749-1581

DOI - 10.1002/mrc.4508

Subject(s) - chemistry , oligomer , alkylation , histone octamer , dna , combinatorial chemistry , computational chemistry , mechanism of action , nuclear magnetic resonance spectroscopy , mechanism (biology) , stereochemistry , organic chemistry , biochemistry , nucleosome , histone , catalysis , in vitro , philosophy , epistemology

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.

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