title: Inhibition of heat shock transcription factor binding by a linear polyamide binding in an unusual 1:1 mode.
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.
authors.affiliation: Department of Chemistry, Washington University, St. Louis, MO 63130, USA.
authors.forename: Rongsheng E
authors.initials: RE
authors.lastname: Wang
authors.forename: Raj K
authors.initials: RK
authors.lastname: Pandita
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Cai
authors.forename: Clayton R
authors.initials: CR
authors.lastname: Hunt
authors.forename: John-Stephen
authors.initials: JS
authors.lastname: Taylor
mesh_terms: D001665:Binding Sites / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics; D000076249:Heat Shock Transcription Factors; D006801:Humans; D015394:Molecular Structure; D009757:Nylons / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D020033:Protein Isoforms / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics; D013329:Structure-Activity Relationship; D014157:Transcription Factors / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; C000619706:HSF1 protein, human; D000076249:Heat Shock Transcription Factors; D009757:Nylons; D020033:Protein Isoforms; D014157:Transcription Factors