title: An anthraquinone scaffold for putative, two-face Bim BH3 α-helix mimic.
abstract: Bim BH3 peptide features an α-helix with hotspot residues on multiple faces. Compound 5 (6-bromo-2,3-dihydroxyanthracene-9,10-dione), which adopts a rigid-plan amphipathic conformation, was designed and evaluated as a scaffold to mimic two faces of Bim α-helix. It reproduced the functionalities of both D67 and I65 on two opposing helical sides. Moreover, it maintained the two-faced binding mode during further evolution. A putative BH3 α-helix mimic and nanomolar Bcl-2/Mcl-1 dual inhibitor, 6, was obtained based on the structure of 5.
authors.affiliation: State Key Laboratory of Fine Chemicals, School of Chemistry, Dalian University of Technology, Dalian 116012, People's Republic of China. zczhang@dlut.edu.cn
authors.forename: Zhichao
authors.initials: Z
authors.lastname: Zhang
authors.forename: Xiangqian
authors.initials: X
authors.lastname: Li
authors.forename: Ting
authors.initials: T
authors.lastname: Song
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhao
authors.forename: Yingang
authors.initials: Y
authors.lastname: Feng
mesh_terms: D000880:Anthraquinones / Q000737:chemistry*; D051017:Apoptosis Regulatory Proteins / Q000737:chemistry*; D000072224:Bcl-2-Like Protein 11; D002851:Chromatography, High Pressure Liquid; D008565:Membrane Proteins / Q000737:chemistry*; D008958:Models, Molecular; D018716:Molecular Mimicry; D019906:Nuclear Magnetic Resonance, Biomolecular; D010446:Peptide Fragments / Q000737:chemistry*; D011518:Proto-Oncogene Proteins / Q000737:chemistry*
chemical_list: D000880:Anthraquinones; D051017:Apoptosis Regulatory Proteins; C474007:Bax protein (53-86); D000072224:Bcl-2-Like Protein 11; D008565:Membrane Proteins; D010446:Peptide Fragments; D011518:Proto-Oncogene Proteins