Two‐Face,Two‐Turn α‐Helix Mimetics Based on a Cross‐Acridine Scaffold: Analogues of the Bim BH3 Domain |
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| Authors: | Xiangqian Li Ziqian Wang Prof Yingang Feng Ting Song Pengchen Su Chengbin Chen Gaobo Chai Ying Yang Prof Zhichao Zhang |
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| Affiliation: | 1. State Key Laboratory of Fine Chemicals, School of Chemistry, Dalian University of Technology, 2 Linggong Road, Dalian 116012 (P.R. China);2. Shandong Provincial Key Laboratory of Energy Genetics, Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences, 189 Songling Road, Qingdao, Shandong 266101 (P.R. China);3. School of Life Science and Technology, Dalian University of Technology, 2 Linggong Road, Dalian 116024 (P.R. China);4. Public Laboratory of Bioenergy and Biofuels, Qingdao Institute of Bioenergy and Bioprocess Technology, 189 Songling Road, Qingdao, Shandong 266101 (P.R. China) |
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| Abstract: | The design of a cross‐acridine scaffold mimicking the i, i+3, i+5, and i+7 residues distributed over a two‐face, two‐turn α‐helix is described. Docking studies and 2D 1H,15N HSQC NMR spectroscopy provide compelling evidence that compound 3 d accurately reproduces the arrangement of four hotspots in the Bim BH3 peptide to permit binding to the Mcl‐1 and Bcl‐2 proteins (Ki 0.079 and 0.056 μM , respectively). Furthermore, the hotspot mutation could also be mimicked by individual or multiple deletions of side chains on the scaffold. |
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| Keywords: | acridines helical structures Mcl‐1 peptidomimetics two‐face |
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