title: Interaction of Berberine derivative with protein POT1 affect telomere function in cancer cells.
abstract: The protein POT1 plays an important role in telomere protection, which is related with telomere elongation and cell immortality. The protein has been recognized as a promising drug target for cancer treatment. In the present study, we cloned, overexpressed in Escherichia coli for the first time, and purified recombinant human POT1. The protein was proved to be active through filter binding assay, FRET and CD experiments. In the initial screening for protein binding ligands using SPR, compound Sysu-00692 was found to bind well with the POT1, which was confirmed with EMSA. Its in vivo activity study showed that compound Sysu-00692 could interfere with the binding between human POT1 and the telomeric DNA through chromatin immunoprecipitation. Besides, the compound showed mild inhibition on telomerase and cell proliferation. As we know, compound Sysu-00692 is the first reported POT1-binding ligand, which could serve as a lead compound for further improvement. This work offered a potentially new approach for drug design for the treatment of cancers.
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou University City, PR China.
authors.forename: Nannan
authors.initials: N
authors.lastname: Xiao
authors.forename: Siqi
authors.initials: S
authors.lastname: Chen
authors.forename: Yan
authors.initials: Y
authors.lastname: Ma
authors.forename: Jun
authors.initials: J
authors.lastname: Qiu
authors.forename: Jia-Heng
authors.initials: JH
authors.lastname: Tan
authors.forename: Tian-Miao
authors.initials: TM
authors.lastname: Ou
authors.forename: Lian-Quan
authors.initials: LQ
authors.lastname: Gu
authors.forename: Zhi-Shu
authors.initials: ZS
authors.lastname: Huang
authors.forename: Ding
authors.initials: D
authors.lastname: Li
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D001599:Berberine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D047369:Chromatin Immunoprecipitation; D003001:Cloning, Molecular; D004277:DNA, Single-Stranded / Q000378:metabolism; D015195:Drug Design; D031541:Fluorescence Resonance Energy Transfer; D054856:G-Quadruplexes; D006801:Humans; D008024:Ligands; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D000089804:Shelterin Complex; D019098:Telomerase / Q000037:antagonists & inhibitors; D016615:Telomere / Q000378:metabolism*; D034501:Telomere-Binding Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D004277:DNA, Single-Stranded; D008024:Ligands; C440849:POT1 protein, human; D011994:Recombinant Proteins; D000089804:Shelterin Complex; C571899:Sysu-00692; D034501:Telomere-Binding Proteins; D001599:Berberine; D019098:Telomerase