Details
| Original language | English |
|---|---|
| Pages (from-to) | 1308-1315 |
| Number of pages | 8 |
| Journal | ACS chemical biology |
| Volume | 12 |
| Issue number | 5 |
| Publication status | Published - 19 May 2017 |
Abstract
A human telomere sequence that folds into an intramolecular (3 + 1)-hybrid G-quadruplex was modified by the incorporation of 2′-fluoro-2′-deoxyriboguanosines ( FG) into syn positions of its outer tetrad. A circular dichroism and NMR spectral analysis reveals a nearly quantitative switch of the G-tetrad polarity with concerted syn↔anti transitions of all four G residues. These observations follow findings on a FG-substituted (3 + 1)-hybrid quadruplex with a different fold, suggesting a more general propensity of hybrid-type quadruplexes to undergo a tetrad polarity reversal. Two out of the three FG analogs in both modified quadruplexes adopt an S-type sugar pucker, challenging a sole contribution of N-type sugars in enforcing an anti glycosidic torsion angle associated with the tetrad flip. NMR restrained three-dimensional structures of the two substituted quadruplexes reveal a largely conserved overall fold but significant rearrangements of the overhang and loop nucleotides capping the flipped tetrad. Sugar pucker preferences of the FG analogs may be rationalized by different orientations of the fluorine atom and its resistance to be positioned within the narrow groove with its highly negative electrostatic potential and spine of water molecules.
Cite this
- Standard
- Harvard
- Apa
- Vancouver
- BibTeX
- RIS
In: ACS chemical biology, Vol. 12, No. 5, 19.05.2017, p. 1308-1315.
Research output: Contribution to journal › Article › Research › peer review
}
TY - JOUR
T1 - Tracing Effects of Fluorine Substitutions on G-Quadruplex Conformational Changes
AU - Dickerhoff, Jonathan
AU - Haase, Linn
AU - Langel, Walter
AU - Weisz, Klaus
N1 - Publisher Copyright: © 2017 American Chemical Society.
PY - 2017/5/19
Y1 - 2017/5/19
N2 - A human telomere sequence that folds into an intramolecular (3 + 1)-hybrid G-quadruplex was modified by the incorporation of 2′-fluoro-2′-deoxyriboguanosines ( FG) into syn positions of its outer tetrad. A circular dichroism and NMR spectral analysis reveals a nearly quantitative switch of the G-tetrad polarity with concerted syn↔anti transitions of all four G residues. These observations follow findings on a FG-substituted (3 + 1)-hybrid quadruplex with a different fold, suggesting a more general propensity of hybrid-type quadruplexes to undergo a tetrad polarity reversal. Two out of the three FG analogs in both modified quadruplexes adopt an S-type sugar pucker, challenging a sole contribution of N-type sugars in enforcing an anti glycosidic torsion angle associated with the tetrad flip. NMR restrained three-dimensional structures of the two substituted quadruplexes reveal a largely conserved overall fold but significant rearrangements of the overhang and loop nucleotides capping the flipped tetrad. Sugar pucker preferences of the FG analogs may be rationalized by different orientations of the fluorine atom and its resistance to be positioned within the narrow groove with its highly negative electrostatic potential and spine of water molecules.
AB - A human telomere sequence that folds into an intramolecular (3 + 1)-hybrid G-quadruplex was modified by the incorporation of 2′-fluoro-2′-deoxyriboguanosines ( FG) into syn positions of its outer tetrad. A circular dichroism and NMR spectral analysis reveals a nearly quantitative switch of the G-tetrad polarity with concerted syn↔anti transitions of all four G residues. These observations follow findings on a FG-substituted (3 + 1)-hybrid quadruplex with a different fold, suggesting a more general propensity of hybrid-type quadruplexes to undergo a tetrad polarity reversal. Two out of the three FG analogs in both modified quadruplexes adopt an S-type sugar pucker, challenging a sole contribution of N-type sugars in enforcing an anti glycosidic torsion angle associated with the tetrad flip. NMR restrained three-dimensional structures of the two substituted quadruplexes reveal a largely conserved overall fold but significant rearrangements of the overhang and loop nucleotides capping the flipped tetrad. Sugar pucker preferences of the FG analogs may be rationalized by different orientations of the fluorine atom and its resistance to be positioned within the narrow groove with its highly negative electrostatic potential and spine of water molecules.
UR - http://www.scopus.com/inward/record.url?scp=85019631925&partnerID=8YFLogxK
U2 - 10.1021/acschembio.6b01096
DO - 10.1021/acschembio.6b01096
M3 - Article
VL - 12
SP - 1308
EP - 1315
JO - ACS chemical biology
JF - ACS chemical biology
SN - 1554-8929
IS - 5
ER -