Inhibition of heat shock transcription factor binding by a linear polyamide binding in an unusual 1:1 mode

Chembiochem. 2012 Jan 2;13(1):97-104. doi: 10.1002/cbic.201100524. Epub 2011 Dec 1.

Abstract

Heat shock proteins (HSPs) are known to protect cells from heat, oxidative stress, and the cytotoxic effects of drugs, and thus can enhance cancer cell survival. As a result, HSPs are a newly emerging class of protein targets for chemotherapy. Among the various HSPs, the HSP70 family is the most highly conserved and prevalent. Herein we describe the development of a β-alanine rich linear polyamide that binds the GGA heat shock elements (HSEs) 3 and 4 in the HSP70 promoter in an unusual 1:1 mode and inhibits heat shock transcription factor 1 (HSF1) binding in vitro.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Binding Sites / drug effects
  • DNA-Binding Proteins / antagonists & inhibitors*
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / genetics
  • Heat Shock Transcription Factors
  • Humans
  • Molecular Structure
  • Nylons / chemical synthesis
  • Nylons / chemistry
  • Nylons / pharmacology*
  • Protein Isoforms / antagonists & inhibitors
  • Protein Isoforms / chemistry
  • Protein Isoforms / genetics
  • Structure-Activity Relationship
  • Transcription Factors / antagonists & inhibitors*
  • Transcription Factors / chemistry
  • Transcription Factors / genetics

Substances

  • DNA-Binding Proteins
  • HSF1 protein, human
  • Heat Shock Transcription Factors
  • Nylons
  • Protein Isoforms
  • Transcription Factors