Structural development of stabilized helical peptides as inhibitors of estrogen receptor (ER)-mediated transcription. Issue 15 (1st August 2015)

• Record Type: Journal Article
• Authors: Demizu, Yosuke; Misawa, Takashi; Nagakubo, Takaya; Kanda, Yasunari; Okuhira, Keiichiro; Sekino, Yuko; Naito, Mikihiko; Kurihara, Masaaki
• Is Part Of: Bioorganic & medicinal chemistry. Volume 23:Issue 15(2015)
• Page Start: 4132
• Page End: 4138
• Publication Date: 2015-08-01
• Subjects: Estrogen receptor -- Protein–protein interaction -- Transcriptional inhibitor -- Helical peptide; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2015.06.067
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Abstract: Three types of stabilized helical peptides containing disulfide bonds, C–C cross-linked side chains, or α, α-disubstituted amino acids (2-aminoisobutyric acid (Aib)) were designed and synthesized as inhibitors of estrogen receptor (ER)-coactivator interactions. Furthermore, heptaarginine (R7)-conjugated versions of the peptides were prepared, and their effects on ER-mediated transcription were evaluated at the cellular level (in ER-positive T47D cells). Among them, the R7-conjugated peptides 11 and 12 downregulated the mRNA expression of pS2 (an ER-mediated gene whose expression is upregulated by 17β-estradiol) by 95% (at a dose of 10 μM) and 87% (at a dose of 3 μM), respectively.