title: Boronic Acid-Appended Molecular Glues for ATP-Responsive Activity Modulation of Enzymes.
abstract: Water-soluble linear polymers GumBAn (m/n = 18/6, 12/12, and 6/18) with multiple guanidinium ion (Gu(+)) and boronic acid (BA) pendants in their side chains were synthesized as ATP-responsive modulators for enzyme activity. GumBAn polymers strongly bind to the phosphate ion (PO4(-)) and 1,2-diol units of ATP via the Gu(+) and BA pendants, respectively. As only the Gu(+) pendants can be used for proteins, GumBAn is able to modulate the activity of enzymes in response to ATP. As a proof-of-concept study, we demonstrated that trypsin (Trp) can be deactivated by hybridization with GumBAn. However, upon addition of ATP, Trp was liberated to retrieve its hydrolytic activity due to a higher preference of GumBAn toward ATP than Trp. This event occurred in a much lower range of [ATP] than reported examples. Under cellular conditions, the hydrolytic activity of Trp was likewise modulated.
authors.affiliation: Department of Chemistry and Biotechnology, School of Engineering, The University of Tokyo , 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
authors.forename: Kou
authors.initials: K
authors.lastname: Okuro
authors.affiliation: Department of Chemistry and Biotechnology, School of Engineering, The University of Tokyo , 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
authors.forename: Mizuki
authors.initials: M
authors.lastname: Sasaki
authors.affiliation: Department of Chemistry and Biotechnology, School of Engineering, The University of Tokyo , 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.|RIKEN Center for Emergent Matter Science , 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
authors.forename: Takuzo
authors.initials: T
authors.lastname: Aida
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry*; D001897:Boronic Acids / Q000737:chemistry*; D013050:Spectrometry, Fluorescence; D014357:Trypsin / Q000737:chemistry*
chemical_list: D001897:Boronic Acids; D000255:Adenosine Triphosphate; D014357:Trypsin