Details
| Original language | English |
|---|---|
| Pages (from-to) | 985-993 |
| Number of pages | 9 |
| Journal | CHEMBIOCHEM |
| Volume | 20 |
| Issue number | 8 |
| Early online date | 4 Dec 2018 |
| Publication status | Published - 15 Apr 2019 |
| Externally published | Yes |
Abstract
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.
Keywords
- G-quadruplexes, aptamers, conformation analysis, guanosine, oligonucleotides, topology
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Biochemistry
- Biochemistry, Genetics and Molecular Biology(all)
- Molecular Medicine
- Biochemistry, Genetics and Molecular Biology(all)
- Molecular Biology
- Chemistry(all)
- Organic Chemistry
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In: CHEMBIOCHEM, Vol. 20, No. 8, 15.04.2019, p. 985-993.
Research output: Contribution to journal › Article › Research › peer review
}
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 -