Macrocyclic and Helical Oligoamides as a New Class of G-Quadruplex Ligands

Abstract

A planar trimeric macrocyclic oligoamide of 8-amino-2-quinoline carboxylic acid, bearing ammonium side chains, stabilizes the human telomeric G-quadruplex more strongly than the potent ligand telomestatin. Furthermore, a helical oligoamide tetramer also binds strongly to G-quadruplexes and is a new structural class of quadruplex ligand that appears to interact enantioselectively.

Synthesis of Bis‐indole Carboxamides as G‐Quadruplex Stabilizing and Inducing Ligands

“…It shows maximum stabilisation potential for c-kit2 quadruplex (DT m = 21.7 K at 1 mm, that is a T m of 93 8C) comparable to the data obtained for the natural product telomestatin (DT m = 20.4 K at 1 mm). [18] By altering the side chain to a N,N-dimethylaminoethyl group (1 b), a diminished stabilisation for quadruplex sequences was observed (Figure 2 A, Table 2). Ligand 1 b shows a DT m of 16.6 K at 1 mm for both c-kit2 and h-telo quadruplex sequences.…”

Platinum(II) Phenanthroimidazoles for Targeting Telomeric G‐Quadruplexes

“…This is consistent with a binding stoichiometry of 2:1, a value that has previously been reported for other strong G4 binders, such as telomestatin [21] and a macrocyclic oligoamide. [21,22] We next examined the binding affinity of complex 1 to the G-quadruplex using a fluorescence intercalator displacement (FID) assay. This experiment is based on previous work by Teulade-Fichou and co-workers.…”

Large-scale and chromatography-free synthesis of an octameric quinoline-based aromatic amide helical foldamer

“…Thus, amphipathic aryl amide oligomers have been fine-tuned to show selective antimicrobial activity 23 or to interfere with heparin function 24 . Linear aryl amides have been used as α-helix mimetics designed to disrupt protein-protein interactions 25,26 , and helical oligomers bearing cationic side chains feature cell-penetrating properties 27,28 and selective binding to G-quadruplex DNA 29,30 .…”

“…Second, the same procedures serve, after some adjustments, to produce variants having other side chains than isobutoxy groups, including water-solubilizing side chains (see Experimental design). For example, a variant of the helical octamer bearing ornithine-like ammonium side chains shows promise for several biological applications [27][28][29][30] , and a variant bearing oligoethylene oxide side chains was recently prepared to be endowed with solubility in a broad range of media 32 . Anionic, aspartate-like side chains have been introduced as well 30,33 .…”