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Updated: Jun 2, 2026

In Vitro Chemical Mapping of G-Quadruplex DNA Structures by Bis-3-Chloropiperidines
Published on: May 12, 2023
Acridine and quindoline oligomers linked through a 4-aminoproline backbone prefer G-quadruplex structures
Rubén Ferreira1, Roberto Artali, Josep Farrera-Sinfreu
1Institute for Research in Biomedicine, IQAC-CSIC, CIBER-BBN Networking Centre on Bioengineering, Biomaterials and Nanomedicine, Baldiri Reixac 10, E-08028 Barcelona, Spain. ruben.ferreira@irbbarcelona.org
Background:
DNA-intercalating drugs are planar molecules with several fused aromatic rings that form stacks between DNA base pairs, reducing the opening and unwinding of the double helix. Recently, interest on intercalating agents has moved in the search for new ligands to G-quadruplex structures.
Methods:
The DNA binding properties of 4-aminoproline oligomers functionalized with one, two or three units of acridine and/or quindoline have been analyzed by competitive dialysis. A NMR/molecular dynamics study was performed on G-quadruplex telomeric sequence and the 4-aminoproline dimer carrying two quindolines. A model of the complex with the telomeric DNA quadruplex is described.
Results And Conclusions:
A selectivity of quindoline 4-aminoproline oligomers for G-quadruplex and triplex structures was observed, especially for those quadruplex sequences found in telomeres and in the promoter regions of c-myc and bcl-2 oncogenes. In this model the quindoline dimer is stabilized by π-π stacking interactions between the aromatic rings of the ligand and the nucleobases of the telomeric sequence that are located above and below the molecule.
General Significance:
The results of this work can be used for the design of new molecules with high affinity to telomeres which may have anticancer properties.
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