title: Improving the Solubility of Artificial Ligands of Streptavidin to Enable More Practical Reversible Switching of Protein Localization in Cells.
abstract: Chemical inducers that can control target-protein localization in living cells are powerful tools to investigate dynamic biological systems. We recently reported the retention using selective hook or "RUSH" system for reversible localization change of proteins of interest by addition/washout of small-molecule artificial ligands of streptavidin (ALiS). However, the utility of previously developed ALiS was restricted by limited solubility in water. Here, we overcame this problem by X-ray crystal structure-guided design of a more soluble ALiS derivative (ALiS-3), which retains sufficient streptavidin-binding affinity for use in the RUSH system. The ALiS-3-streptavidin interaction was characterized in detail. ALiS-3 is a convenient and effective tool for dynamic control of α-mannosidase II localization between ER and Golgi in living cells.
authors.affiliation: Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Tachibana
authors.affiliation: Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.|Present address: Graduate School of Science and Engineering, Saitama University, 255 Shimo-Okubo, Sakura-ku, Saitama City, Saitama, 338-8570, Japan.
authors.forename: Takuya
authors.identifier: 0000-0002-3425-3589
authors.initials: T
authors.lastname: Terai
authors.affiliation: Institut Curie, Centre de Recherche, PSL Research University, 26, rue d'Ulm, Paris, 75248, France.|CNRS, UMR144, PSL Research University, 26, rue d'Ulm, Paris, 75248, France.
authors.forename: Gaelle
authors.initials: G
authors.lastname: Boncompain
authors.affiliation: Graduate School of Science, Osaka University, 2-1 Yamadaoka, Suita, Osaka, 565-0871, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Sugiyama
authors.affiliation: Drug Discovery Initiative, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.
authors.forename: Nae
authors.initials: N
authors.lastname: Saito
authors.affiliation: Institut Curie, Centre de Recherche, PSL Research University, 26, rue d'Ulm, Paris, 75248, France.|CNRS, UMR144, PSL Research University, 26, rue d'Ulm, Paris, 75248, France.
authors.forename: Franck
authors.identifier: 0000-0002-9129-9401
authors.initials: F
authors.lastname: Perez
authors.affiliation: Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.|Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.|CREST, JST, 7 Gobancho, Chiyoda-ku, Tokyo, 102-0076, Japan.
authors.forename: Yasuteru
authors.initials: Y
authors.lastname: Urano
mesh_terms: D001665:Binding Sites; D003460:Crystallization; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D009025:Morpholines / Q000737:chemistry / Q000378:metabolism; D010795:Phthalic Acids / Q000737:chemistry* / Q000494:pharmacology; D011485:Protein Binding; D021381:Protein Transport / Q000502:physiology*; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D011728:Pyridones / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D012833:Siloxanes / Q000737:chemistry / Q000378:metabolism; D012995:Solubility; D019809:Streptavidin / Q000737:chemistry* / Q000378:metabolism; D013449:Sulfonamides / Q000737:chemistry* / Q000378:metabolism; D000096926:Benzenesulfonamides
chemical_list: D008024:Ligands; D009025:Morpholines; D010795:Phthalic Acids; D011506:Proteins; D011728:Pyridones; D012833:Siloxanes; D019809:Streptavidin; D013449:Sulfonamides; C528071:1,3-dimethyl-1,3-p-fluorophenyl-1,3-(3-morpholinopropyl)-1,3-disiloxane; C000621034:ALiS-3 compound; D000096926:Benzenesulfonamides; C000621035:ALiS-6 compound
keywords: bioorganic chemistry; heterocycles; ligand design; protein structures; streptavidin