title: Combinatorial screening for specific drug solubilizers with switchable release profiles.
abstract: Polymer-block-peptide conjugates are tailored to render hydrophobic small molecule drugs water soluble. The combinatorial strategy selects for bioconjugates that exhibit sequence-specific solubilization and switchable release profiles of the cargo through incorporation of a disulfide linker moiety into the peptide-library design. While the study focused on the photosensitizer m-THPC and reductive carrier cleavage, the approach is generic and might be expanded toward a broad range of poorly soluble small-molecule drugs and other selective cleavage mechanisms to disassemble a peptide binding domain of the bioconjugate-based solubilizer.
authors.affiliation: Laboratory for Organic Synthesis of Functional Systems, Department of Chemistry, Humboldt-Universität zu Berlin, Brook-Taylor-Str. 2, D-12489, Berlin, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Wieczorek
authors.forename: Sara
authors.initials: S
authors.lastname: Vigne
authors.forename: Tiziana
authors.initials: T
authors.lastname: Masini
authors.forename: Daniela
authors.initials: D
authors.lastname: Ponader
authors.forename: Laura
authors.initials: L
authors.lastname: Hartmann
authors.forename: Anna K H
authors.initials: AK
authors.lastname: Hirsch
authors.forename: Hans G
authors.initials: HG
authors.lastname: Börner
mesh_terms: D000595:Amino Acid Sequence; D016503:Drug Delivery Systems / Q000379:methods*; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D008652:Mesoporphyrins / Q000737:chemistry*; D008856:Microscopy, Fluorescence; D008958:Models, Molecular; D008969:Molecular Sequence Data; D050997:Nanomedicine / Q000379:methods / Q000639:trends; D010455:Peptides / Q000737:chemistry* / Q000235:genetics; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D017319:Photosensitizing Agents / Q000737:chemistry*; D017422:Sequence Analysis, DNA; D012995:Solubility
chemical_list: D008652:Mesoporphyrins; D010455:Peptides; D004364:Pharmaceutical Preparations; D017319:Photosensitizing Agents; C072269:temoporfin
keywords: PEG; drug delivery; drug formulation; peptide; stimuli responsive