title: Structure-activity relationship of benzodiazepine derivatives as LXXLL peptide mimetics that inhibit the interaction of vitamin D receptor with coactivators.
abstract: Suppression of vitamin D receptor (VDR)-mediated transcription is expected to be of therapeutic value in Paget's disease of bone. It is known that interaction between VDR and coactivators is necessary for VDR transactivation, and the interaction occurs when VDR recognizes an LXXLL peptide motif of coactivators. We previously reported that benzodiazepine derivatives designed as LXXLL peptide mimetics inhibited the interaction of VDR and coactivators, and reduced VDR transcription. Here, we investigated the structure-activity relationship of 7- and 8-substituted benzodiazepine derivatives, and established that the amino group at the 8-position is critical for the inhibitory activity.
authors.affiliation: Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Mita
authors.forename: Kosuke
authors.initials: K
authors.lastname: Dodo
authors.forename: Tomomi
authors.initials: T
authors.lastname: Noguchi-Yachide
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Hashimoto
authors.forename: Minoru
authors.initials: M
authors.lastname: Ishikawa
mesh_terms: D000595:Amino Acid Sequence; D001569:Benzodiazepines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D001665:Binding Sites; D040761:Biomimetic Materials / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D062105:Molecular Docking Simulation; D010455:Peptides / Q000737:chemistry*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D018167:Receptors, Calcitriol / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D013329:Structure-Activity Relationship; D015533:Transcriptional Activation / Q000187:drug effects
chemical_list: D010455:Peptides; D018167:Receptors, Calcitriol; D001569:Benzodiazepines