Title
Loop Length Affects Syn‐Anti Conformational Rearrangements in Parallel G‐Quadruplexes
Author
Beatrice Karg, Klaus Weisz
Year
2018
Journal
Chemistry A European Journal
Abstract
A G‐quadruplex forming sequence from the MYC promoter region was modified with syn‐favoring 8‐bromo‐2'‐deoxyguanosine residues. Depending on the number and position of modifications in the intramolecular parallel G‐quadruplex, substitutions with the bromoguanosine analog at the 5'‐tetrad induce conformational rearrangements with concerted all‐anti to all‐syn transitions for all residues of the modified G‐quartet. No unfavorable steric interactions of the C8‐substituents in the medium grooves are apparent in the high‐resolution structure as determined for a tetrasubstituted MYC quadruplex that exclusively forms the all‐syn isomer. In contrast, considerable steric clashes with 5'‐phosphate oxygen atoms for those analogs that follow a less flexible 1‐nucleotide loop in the native all‐anti conformation seem to constitute the major driving force for the tetrad inversion and allow for the rational design of appropriately substituted sequences. Correlations found between the population of species subjected to a tetrad flip and melting temperatures indicate that more effective conformational transitions are compromised by lower thermal stabilities of the modified parallel quadruplexes.
Instrument
J-810
Keywords
Circular dichroism, DNA structure, Biochemistry