TY - JOUR

T1 - Triggering G-Quadruplex Conformation Switching with [7]Helicenes

AU - Lousen, Bodil

AU - Pedersen, Stephan K.

AU - Rasadean, Dora M.

AU - Pantos, G. Dan

AU - Pittelkow, Michael

PY - 2021

Y1 - 2021

N2 - The dynamic interplay between two types of chiral structures; fully conjugated racemic hetero[7]helicenes and DNA strands prone to fold into G-quadruplex structures is described. Both the [7]helicenes and the G-quadruplex DNA structures exist in more than one conformation in solution. We show that the structures interact with and stabilise each other, mutually amplifying and stabilising certain conformations at increased temperatures. The [7]helicene ligands L1 and L2 stabilise the parallel conformation of k-ras significantly, whereas hybrid (K+) and antiparallel (Na+) h-telo G-quadruplexes are stabilised upon conformational switching into altered G-quadruplex conformations. Both L1 and L2 induce parallel G-quadruplexes from hybrid structures (K+) and L1 induces hybrid G-quadruplexes from antiparallel conformations (Na+). Enantioselective binding of one helicene enantiomer is observed for helicene ligand L2, and VTCD melting experiments are used to estimate the racemisation barrier of the helicene.

AB - The dynamic interplay between two types of chiral structures; fully conjugated racemic hetero[7]helicenes and DNA strands prone to fold into G-quadruplex structures is described. Both the [7]helicenes and the G-quadruplex DNA structures exist in more than one conformation in solution. We show that the structures interact with and stabilise each other, mutually amplifying and stabilising certain conformations at increased temperatures. The [7]helicene ligands L1 and L2 stabilise the parallel conformation of k-ras significantly, whereas hybrid (K+) and antiparallel (Na+) h-telo G-quadruplexes are stabilised upon conformational switching into altered G-quadruplex conformations. Both L1 and L2 induce parallel G-quadruplexes from hybrid structures (K+) and L1 induces hybrid G-quadruplexes from antiparallel conformations (Na+). Enantioselective binding of one helicene enantiomer is observed for helicene ligand L2, and VTCD melting experiments are used to estimate the racemisation barrier of the helicene.

KW - chirality

KW - circular dichroism

KW - conformational analysis

KW - G-quadruplexes

KW - helical structures

U2 - 10.1002/chem.202004990

DO - 10.1002/chem.202004990

M3 - Journal article

C2 - 33326174

VL - 27

SP - 6064

EP - 6069

JO - Chemistry: A European Journal

JF - Chemistry: A European Journal

SN - 0947-6539

IS - 19

ER -