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Fluorine‐Mediated Editing of a G‐Quadruplex Folding Pathway
Author(s) -
Dickerhoff Jonathan,
Weisz Klaus
Publication year - 2018
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201800099
Subject(s) - g quadruplex , chemistry , hydrogen bond , guanosine , folding (dsp implementation) , stereochemistry , fluorine , molecule , biochemistry , dna , organic chemistry , electrical engineering , engineering
A (3+1)‐hybrid‐type G‐quadruplex was substituted within its central tetrad by a single 2′‐fluoro‐modified guanosine. Driven by the anti ‐favoring nucleoside analogue, a novel quadruplex fold with inversion of a single G‐tract and conversion of a propeller loop into a lateral loop emerges. In addition, scalar couplings across hydrogen bonds demonstrate the formation of intra‐ and inter‐residual F ⋅⋅⋅ H8−C8 pseudo‐hydrogen bonds within the modified quadruplexes. Alternative folding can be rationalized by the impact of fluorine on intermediate species on the basis of a kinetic partitioning mechanism. Apparently, chemical or other environmental perturbations are able to redirect folding of a quadruplex, possibly modulating its regulatory role in physiological processes.