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FerryCalin: an Engineered Lipocalin Protein Directed against the Transferrin Receptor with Potential for Brain Drug Delivery.
Nästle, Lea; Deuschle, Friedrich-Christian; Morath, Volker; Skerra, Arne.
Afiliación
  • Nästle L; Lehrstuhl für Biologische Chemie, Technische Universität München, 85354, Freising, Germany.
  • Deuschle FC; Lehrstuhl für Biologische Chemie, Technische Universität München, 85354, Freising, Germany.
  • Morath V; Lehrstuhl für Biologische Chemie, Technische Universität München, 85354, Freising, Germany.
  • Skerra A; Lehrstuhl für Biologische Chemie, Technische Universität München, 85354, Freising, Germany.
Chembiochem ; 24(10): e202200795, 2023 05 16.
Article en En | MEDLINE | ID: mdl-37005222
ABSTRACT
The transferrin receptor (TfR) mediates transcytosis across the blood-brain barrier (BBB), which offers a promising approach for the non-invasive delivery of therapeutics into the brain parenchyma. Employing the recombinant homodimeric murine TfR ectodomain, prepared in a biochemically functional state, we have selected a cognate Anticalin via phage display and bacterial cell surface display from a random library based on the human lipocalin 2 (Lcn2). After affinity maturation, several engineered lipocalin variants were identified that bind murine TfR in a non-competitive manner with the natural ligand (transferrin ⋅ Fe3+ ), among those an Anticalin - dubbed FerryCalin - exhibiting a dissociation constant (KD ) of 3.8 nM. Epitope analysis using the SPOT technique revealed a sequential epitope in a surface region of TfR remote from the transferrin-binding site. Due to the fast kon rate and short complex half-life, as evidenced by real-time surface plasmon resonance (SPR) measurements, FerryCalin, or one of its related mutants, shows characteristics as a potential vehicle for the brain delivery of biopharmaceuticals.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Receptores de Transferrina / Lipocalinas Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Chembiochem Asunto de la revista: BIOQUIMICA Año: 2023 Tipo del documento: Article País de afiliación: Alemania

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Receptores de Transferrina / Lipocalinas Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Chembiochem Asunto de la revista: BIOQUIMICA Año: 2023 Tipo del documento: Article País de afiliación: Alemania