TY - JOUR

T1 - DNA–RNA Hybrid Quadruplexes Reveal Interactions that Favor RNA Parallel Topologies

AU - Haase, Linn

AU - Dickerhoff, Jonathan

AU - Weisz, Klaus

N1 - Publisher Copyright: © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

PY - 2018/10/12

Y1 - 2018/10/12

N2 - A DNA G-quadruplex adopting a (3+1)-hybrid structure was substituted at its 5′-tetrad by riboguanosine (rG) analogs. Incorporation of anti-favoring rG at appropriate syn-positions of the 5′-outer tetrad induced conformational rearrangements to yield a quadruplex featuring a 5′-tetrad with reversed polarity. A high-resolution structure of a disubstituted quadruplex variant as well as direct NMR experimental evidence reveals a non-conventional C−H⋅⋅⋅O hydrogen bond in a medium groove between the 2′-OH of an rG residue adopting a C2′-endo sugar pucker and H8 of a 3′-neighboring anti-G residue. In contrast, a C3′-endo sugar conformation for another guanine ribonucleotide prevents formation of a corresponding hydrogen bond but relocates its 2′-OH substituent from the quadruplex narrow groove into a medium groove. Both the formation of favorable CHO hydrogen bridges and unfavorable interactions of the 2′-hydroxyl group in a narrow groove will promote RNA folding into a parallel topology featuring all-anti core residues and four grooves of medium size.

AB - A DNA G-quadruplex adopting a (3+1)-hybrid structure was substituted at its 5′-tetrad by riboguanosine (rG) analogs. Incorporation of anti-favoring rG at appropriate syn-positions of the 5′-outer tetrad induced conformational rearrangements to yield a quadruplex featuring a 5′-tetrad with reversed polarity. A high-resolution structure of a disubstituted quadruplex variant as well as direct NMR experimental evidence reveals a non-conventional C−H⋅⋅⋅O hydrogen bond in a medium groove between the 2′-OH of an rG residue adopting a C2′-endo sugar pucker and H8 of a 3′-neighboring anti-G residue. In contrast, a C3′-endo sugar conformation for another guanine ribonucleotide prevents formation of a corresponding hydrogen bond but relocates its 2′-OH substituent from the quadruplex narrow groove into a medium groove. Both the formation of favorable CHO hydrogen bridges and unfavorable interactions of the 2′-hydroxyl group in a narrow groove will promote RNA folding into a parallel topology featuring all-anti core residues and four grooves of medium size.

KW - DNA–RNA hybrids

KW - G-quadruplexes

KW - NMR spectroscopy

KW - glycosidic torsion angle

KW - pseudo-hydrogen bonds

UR - http://www.scopus.com/inward/record.url?scp=85053380813&partnerID=8YFLogxK

U2 - 10.1002/chem.201803367

DO - 10.1002/chem.201803367

M3 - Article

VL - 24

SP - 15365

EP - 15371

JO - Chemistry - A European Journal

JF - Chemistry - A European Journal

SN - 0947-6539

IS - 57

ER -