TY - JOUR

T1 - Sugar Puckering Drives G‐Quadruplex Refolding: Implications for V‐Shaped Loops

AU - Haase, Linn

AU - Dickerhoff, Jonathan

AU - Weisz, Klaus

N1 - Funding Information: This research was supported by the Deutsche Forschungsgemeinschaft (grant no. WE 1933/15-1).

PY - 2020/1/7

Y1 - 2020/1/7

N2 - A DNA G-quadruplex adopting a (3+1) hybrid structure was modified in two adjacent syn positions of the antiparallel strand with anti-favoring 2′-deoxy-2′-fluoro-riboguanosine ( FrG) analogues. The two substitutions promoted a structural rearrangement to a topology with the 5′-terminal G residue located in the central tetrad and the two modified residues linked by a V-shaped zero-nucleotide loop. Strikingly, whereas a sugar pucker in the preferred north domain is found for both modified nucleotides, the FrG analogue preceding the V-loop is forced to adopt the unfavored syn conformation in the new quadruplex fold. Apparently, a preferred C3′-endo sugar pucker within the V-loop architecture outweighs the propensity of the FrG analogue to adopt an anti glycosidic conformation. Refolding into a V-loop topology is likewise observed for a sequence modified at corresponding positions with two riboguanosine substitutions. In contrast, 2′-F-arabinoguanosine analogues with their favored south-east sugar conformation do not support formation of the V-loop topology. Examination of known G-quadruplexes with a V-shaped loop highlights the critical role of the sugar conformation for this distinct structural motif.

AB - A DNA G-quadruplex adopting a (3+1) hybrid structure was modified in two adjacent syn positions of the antiparallel strand with anti-favoring 2′-deoxy-2′-fluoro-riboguanosine ( FrG) analogues. The two substitutions promoted a structural rearrangement to a topology with the 5′-terminal G residue located in the central tetrad and the two modified residues linked by a V-shaped zero-nucleotide loop. Strikingly, whereas a sugar pucker in the preferred north domain is found for both modified nucleotides, the FrG analogue preceding the V-loop is forced to adopt the unfavored syn conformation in the new quadruplex fold. Apparently, a preferred C3′-endo sugar pucker within the V-loop architecture outweighs the propensity of the FrG analogue to adopt an anti glycosidic conformation. Refolding into a V-loop topology is likewise observed for a sequence modified at corresponding positions with two riboguanosine substitutions. In contrast, 2′-F-arabinoguanosine analogues with their favored south-east sugar conformation do not support formation of the V-loop topology. Examination of known G-quadruplexes with a V-shaped loop highlights the critical role of the sugar conformation for this distinct structural motif.

KW - G-quadruplexes

KW - NMR spectroscopy

KW - V-loop

KW - glycosidic torsion angles

KW - sugar conformation

UR - http://www.scopus.com/inward/record.url?scp=85076545573&partnerID=8YFLogxK

U2 - 10.1002/chem.201904044

DO - 10.1002/chem.201904044

M3 - Article

VL - 26

SP - 524

EP - 533

JO - Chemistry – A European Journal

JF - Chemistry – A European Journal

SN - 1521-3765

IS - 2

ER -