Binding geometries of triple helix selective benzopyrido[4,3-b]indole ligands complexed with double- and triple-helical polynucleotides

S. K. Kim, J. S. Sun, T. Garestier, C. Helene, C. H. Nguyen, E. Bisagni, A. Rodger, B. Norden*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)

Abstract

The binding modes of three benzopyrido[4,3-b]indole derivatives (and one benzo[-f]pyrido[4-3b]quinoxaline derivative) with respect to double helical poly(dA)·poly(dT) and poly[d(A-T)]2 and triple-helical poly(dA)·2poly(dT) have been investigated using linear dichroism (LD) and CD: (I) 3-methoxy-11- amino-BePI where BePI = {7H-8-methyl-benzo[e]pyrido[4,3-b]indole}, (II) 3- methoxy-11-[(3'-amino)propylamino]-BePI, (III) 3-methoxy-7-[(3'- diethylamino)propylamino]BgPI where BgPI = [benzo[g]pyrido[4,3-b]indole], and (IV) 3-methoxy-11-[(3'-amino)propylamino]-BfPQ where BfPQ = {benzo[- f]pyrido[4-3b]quinoxaline}. The magnitudes of the reduced LD of the electronic transitions of the polynucleotide bases and of the bound ligands are generally very similar, suggesting an orientation of the plane of the ligands' fused-ring systems preferentially perpendicular to the helix axis. The LD results suggest that all of the ligands are intercalated for all three polynucleotides. The induced CD spectrum of the BePI chromopore in the (II- BePI)-poly[d(A-T)]2 complex is almost a mirror image of that for the (I- BePI)-poly(dA)·poly(dT) and (I-BePI)-poly(dA)·2poly(dT) complexes, suggesting an antisymmetric orientation of the BePI moiety upon intercalation in poly[d(A-T)]2 compared to the other polynucleotides. The induced CD of I- BePI bound to poly(dA)·2poly(dT) suggests a geometry that is intermediate between that of its other two complexes. The concluded intercalative binding as well as the conformational variations between the different BePI complexes are of interest in relation to the fact that BePI derivatives are triplex stabilizers.

Original languageEnglish
Pages (from-to)101-111
Number of pages11
JournalBiopolymers
Volume42
Issue number1
DOIs
Publication statusPublished - Jul 1997
Externally publishedYes

Keywords

  • Benzo[4,3- b]indole
  • CD
  • DNA ligands
  • Intercalation
  • Linear dichroism
  • Polynucleotides
  • Triple helix stabilization

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