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

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.