title: Thioether side chain cyclization for helical peptide formation: inhibitors of estrogen receptor-coactivator interactions.
abstract: Cystine, lanthionine, and cystathionine containing cyclic peptides incorporating the signature nuclear receptor (NR) box (LXXLL) motif have been synthesized and the abilities of these peptides to inhibit estrogen receptor (ER)-coactivator interactions have been determined. We found that helicity of these peptides directly correlated with their bioactivity. Cystathionine proved to be a redox-stable, isosteric replacement for the cystine disulfide. Cystathionine containing peptide 3 showed higher helical character and a lower inhibition constant (Ki, 7 nm) when compared with its cystine counterpart.
authors.affiliation: Department of Chemistry and the Institute for Molecular Diversity and Drug Design, University of Louisville, Louisville, KY, USA.
authors.forename: A K
authors.initials: AK
authors.lastname: Galande
authors.forename: K S
authors.initials: KS
authors.lastname: Bramlett
authors.forename: T P
authors.initials: TP
authors.lastname: Burris
authors.forename: J L
authors.initials: JL
authors.lastname: Wittliff
authors.forename: A F
authors.initials: AF
authors.lastname: Spatola
mesh_terms: D020816:Amino Acid Motifs; D000603:Amino Acids, Sulfur / Q000737:chemistry*; D001667:Binding, Competitive; D015394:Molecular Structure; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D011960:Receptors, Estrogen / Q000378:metabolism*; D013440:Sulfides / Q000737:chemistry* / Q000494:pharmacology*; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D000603:Amino Acids, Sulfur; D009842:Oligopeptides; D010456:Peptides, Cyclic; D011960:Receptors, Estrogen; D013440:Sulfides; D014157:Transcription Factors