TY - JOUR

T1 - Manipulating DNA G‐Quadruplex Structures by Using Guanosine Analogues

AU - Haase, Linn

AU - Karg, Beatrice

AU - Weisz, Klaus

PY - 2019/4/15

Y1 - 2019/4/15

N2 - The ability to control the folding topology of DNA G-quadruplexes allows for rational design of quadruplex-based scaffolds for potential use in various therapeutic and technological applications. By exploiting the distinct conformational properties of some base- and sugar-modified guanosine surrogates, conformational transitions can be induced through their judicious incorporation at specific sites in the quadruplex core. Changes may involve tetrad polarity inversions with conservation of the global fold or complete refolding to new topologies. Reliable predictions relating to low-energy conformers formed upon specific chemical perturbations of the system and the rational design of modified sequences suffer from our still limited understanding of the subtle interplay of various favorable and unfavorable interactions within a particular quadruplex scaffold. However, aided by an increasing number of systematic substitution experiments and high-resolution structures of modified quadruplex variants, critical interactions, in addition to glycosidic bond angle propensities, are starting to emerge as important contributors to modification-driven quadruplex refolding.

AB - The ability to control the folding topology of DNA G-quadruplexes allows for rational design of quadruplex-based scaffolds for potential use in various therapeutic and technological applications. By exploiting the distinct conformational properties of some base- and sugar-modified guanosine surrogates, conformational transitions can be induced through their judicious incorporation at specific sites in the quadruplex core. Changes may involve tetrad polarity inversions with conservation of the global fold or complete refolding to new topologies. Reliable predictions relating to low-energy conformers formed upon specific chemical perturbations of the system and the rational design of modified sequences suffer from our still limited understanding of the subtle interplay of various favorable and unfavorable interactions within a particular quadruplex scaffold. However, aided by an increasing number of systematic substitution experiments and high-resolution structures of modified quadruplex variants, critical interactions, in addition to glycosidic bond angle propensities, are starting to emerge as important contributors to modification-driven quadruplex refolding.

KW - G-quadruplexes

KW - aptamers

KW - conformation analysis

KW - guanosine

KW - oligonucleotides

KW - topology

UR - http://www.scopus.com/inward/record.url?scp=85061607068&partnerID=8YFLogxK

U2 - 10.1002/cbic.201800642

DO - 10.1002/cbic.201800642

M3 - Article

VL - 20

SP - 985

EP - 993

JO - CHEMBIOCHEM

JF - CHEMBIOCHEM

SN - 1439-4227

IS - 8

ER -