Structural evaluation of tandem hairpin pyrrole-imidazole polyamides recognizing human telomeres

J Am Chem Soc. 2014 Aug 13;136(32):11546-54. doi: 10.1021/ja506058e. Epub 2014 Aug 1.

Abstract

A polyamide containing N-methylpyrrole (Py) and N-methylimidazole (Im), designated PIPA, binds with high affinity and specificity to specific nucleotide sequences in the minor groove of double-helical DNA. Based on a recent report of the synthesis of PIPA for telomere visualization, the present paper focused on the size of the connecting part (hinge region) of two PIPA segments of the tandem hairpin PIPA, Dab(Im-Im-Py)-Py-Py-Py-Im-[Hinge]-Dab(Im-Im-Py)-Py-Py-Py-Im-βAla-NH(CH2)3N(CH3)-(CH2)3NH-[Dye]. The present paper also describes the characterization of binding by measuring the thermal melting temperature and surface plasmon resonance and by specific staining of telomeres (TTAGGG)n in human cells. Microheterogeneity was also investigated by high-resolution mass spectrometry. We found that the optimal compound as the hinge segment for telomere staining was [-NH(C2H4O)2(C2H4)CO-] with tetramethylrhodamine as the fluorescent dye.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA / chemistry
  • Fluorescent Dyes / chemistry
  • HeLa Cells
  • Humans
  • Imidazoles / chemistry*
  • Nylons / chemistry*
  • Protein Binding
  • Pyrroles / chemistry*
  • Rhodamines / chemistry
  • Spectrometry, Mass, Electrospray Ionization
  • Surface Plasmon Resonance
  • Tandem Mass Spectrometry
  • Telomere / chemistry
  • Telomere / ultrastructure*
  • Temperature
  • Thermodynamics
  • Xanthenes / chemistry

Substances

  • Fluorescent Dyes
  • Imidazoles
  • Nylons
  • Pyrroles
  • Rhodamines
  • Xanthenes
  • tetramethylrhodamine
  • Texas red
  • DNA