title: Acridine and quindoline oligomers linked through a 4-aminoproline backbone prefer G-quadruplex structures.
abstract: 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.
  
  
  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.
  
  
  CONCLUSIONS
  The results of this work can be used for the design of new molecules with high affinity to telomeres which may have anticancer properties.
authors.affiliation: Institute 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
authors.forename: Rubén
authors.initials: R
authors.lastname: Ferreira
authors.forename: Roberto
authors.initials: R
authors.lastname: Artali
authors.forename: Josep
authors.initials: J
authors.lastname: Farrera-Sinfreu
authors.forename: Fernando
authors.initials: F
authors.lastname: Albericio
authors.forename: Miriam
authors.initials: M
authors.lastname: Royo
authors.forename: Ramon
authors.initials: R
authors.lastname: Eritja
authors.forename: Stefania
authors.initials: S
authors.lastname: Mazzini
mesh_terms: D000166:Acridines / Q000737:chemistry*; D000470:Alkaloids / Q000737:chemistry*; D004247:DNA / Q000737:chemistry*; D019254:Genes, bcl-2; D016259:Genes, myc; D006801:Humans; D007211:Indoles / Q000737:chemistry*; D008958:Models, Molecular; D015394:Molecular Structure; D011804:Quinolines / Q000737:chemistry*
chemical_list: D000166:Acridines; D000470:Alkaloids; D007211:Indoles; D011804:Quinolines; C522609:acridine-9-carboxylic acid; C016712:quindoline; D004247:DNA