Chemical inhibitors of heat shock protein 70 (HSP70) induction have great potential in antitumor applications such as radiosensitization and chemotherapy. While our attempts to use antisense agents to inhibit HSP70 expression failed, we show that pyrrole-imidazole polyamides can bind effectively to the heat shock promoter and interfere with binding of heat shock transcription factor 1and subsequent expression of HSP70.  Linear polyamides of different designs were synthesized by solid-phase synthesis and their binding affinities to the heat shock element were evaluated by Dnase I footprinting.  Their ability to block heat shock factor 1 binding was demonstrated by an in vitro gel shift assay and the most effective polyamide was shown to decrease HSP70 expression to 55% of its normal level in Jurkat cells by western blot assay.

Development of polyamides as gene inhibitors of heat shock protein 70 expression

240th National Meeting (2010)

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