Photocontrollable sequence-specific DNA alkylation by a pyrrole-imidazole polyamide seco-CBI conjugate

Bioconjug Chem. 2011 Feb 16;22(2):120-4. doi: 10.1021/bc100352y. Epub 2010 Dec 30.

Abstract

We designed and synthesized a Py-Im polyamide seco-CBI conjugate protected by a photocleavable group and demonstrated that it was selectively activated by UV irradiation both in vitro and in vivo. Sequence-specific alkylating Py-Im polyamides containing photolabile linkers may be useful for developing novel chemical- or enzyme-activated anticancer agents and may facilitate spatiotemporal control of gene expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkylation
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology
  • Base Sequence
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • DNA / chemistry*
  • DNA / drug effects
  • Drug Screening Assays, Antitumor
  • Humans
  • Imidazoles / chemistry*
  • Indoles / chemical synthesis
  • Indoles / chemistry*
  • Indoles / pharmacology
  • Molecular Structure
  • Photochemistry
  • Pyrroles / chemical synthesis
  • Pyrroles / chemistry*
  • Pyrroles / pharmacology
  • Stereoisomerism
  • Structure-Activity Relationship
  • Ultraviolet Rays*

Substances

  • Antineoplastic Agents
  • Imidazoles
  • Indoles
  • Pyrroles
  • polyamide 1-(chloromethyl)-5-hydroxyl-1,2-dihydro--3H-benz(e)indole conjugate
  • DNA