title: pH responsive Janus-like supramolecular fusion proteins for functional protein delivery.
abstract: A facile, noncovalent solid-phase immobilization platform is described to assemble Janus-like supramolecular fusion proteins that are responsive to external stimuli. A chemically postmodified transporter protein, DHSA, is fused with (imino)biotinylated cargo proteins via an avidin adaptor with a high degree of spatial control. Notably, the derived heterofusion proteins are able to cross cellular membranes, dissociate at acidic pH due to the iminobiotin linker and preserve the enzymatic activity of the cargo proteins β-galactosidase and the enzymatic subunit of Clostridium botulinum C2 toxin. The mix-and-match strategy described herein opens unique opportunities to access macromolecular architectures of high structural definition and biological activity, thus complementing protein ligation and recombinant protein expression techniques.
authors.affiliation: Institute of Organic Chemistry III, Macromolecular Chemistry, University of Ulm , Albert-Einstein-Allee 11, D-89081 Ulm, Germany.
authors.forename: Seah Ling
authors.initials: SL
authors.lastname: Kuan
authors.forename: David Y W
authors.initials: DY
authors.lastname: Ng
authors.forename: Yuzhou
authors.initials: Y
authors.lastname: Wu
authors.forename: Christina
authors.initials: C
authors.lastname: Förtsch
authors.forename: Holger
authors.initials: H
authors.lastname: Barth
authors.forename: Mikheil
authors.initials: M
authors.lastname: Doroshenko
authors.forename: Kaloian
authors.initials: K
authors.lastname: Koynov
authors.forename: Christoph
authors.initials: C
authors.lastname: Meier
authors.forename: Tanja
authors.initials: T
authors.lastname: Weil
mesh_terms: D000818:Animals; D001710:Biotin / Q000737:chemistry / Q000378:metabolism; D001905:Botulinum Toxins / Q000737:chemistry / Q000378:metabolism*; D045744:Cell Line, Tumor; D006801:Humans; D006863:Hydrogen-Ion Concentration; D046911:Macromolecular Substances / Q000737:chemistry; D008301:Maleimides / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D015394:Molecular Structure; D011092:Polyethylene Glycols / Q000737:chemistry / Q000378:metabolism; D012709:Serum Albumin / Q000737:chemistry / Q000378:metabolism*; D001616:beta-Galactosidase / Q000737:chemistry / Q000378:metabolism*
chemical_list: D046911:Macromolecular Substances; D008301:Maleimides; D012709:Serum Albumin; C043592:maleimide; D011092:Polyethylene Glycols; D001710:Biotin; D001616:beta-Galactosidase; D001905:Botulinum Toxins; C096324:botulinum toxin type C