Anticalin-Proteine als neue Wirkstoffklasse
Für therapeutische Anwendungen
Übersichten
Key WordsAnticalin® | Biopharmazeutikum | Lipocalin | Protein-Design | Proteintherapeutikum
Abstract
Anticalin® proteins as a novel class of drugs
Anticalins constitute a novel class of therapeutically applicable artificial binding proteins. Anticalins are structurally based on the robust scaffold of naturally occurring lipocalin proteins, particularly of human origin, which are responsible for the transport, scavenging or storage of hydrophobic low molecular weight substances in diverse body fluids. Their calyx-like protein architecture is formed by a so called β-barrel consisting of 8 antiparallel β-strands with an adjacent α-helix. While one end of the β-barrel is closed by short peptide loops, 4 structurally variable loops form a pronounced binding pocket at the open end. Combinatorial gene libraries in conjunction with molecular selection techniques enable expansion of the ligand specificity of this protein scaffold beyond low molecular weight haptens to peptides and in particular proteins. High-affinity Anticalin lead candidates have entered different stages of preclinical and clinical development for biomedical applications in the areas of (immuno-)oncology, metabolic as well as respiratory diseases, as antidotes in cases of intoxication and a novel antibiotic. Thus, Anticalins offer an alternative to antibodies with – depending on the application – superior properties.
Korrespondenz:
Prof. Dr. Arne Skerra, Lehrstuhl für Biologische Chemie, Technische Universität München, Emil-Erlenmeyer-Forum 5, 85354 Freising, Germany; e-mail: skerra@tum.de
Zusammenfassung
Anticaline bilden eine neuartige Klasse therapeutisch anwendbarer künstlicher Bindeproteine. Strukturell basieren sie auf der robusten Gerüststruktur natürlich vorkommender, v. a. humaner Lipocalin-Proteine, welche für den Transport, die Abscheidung oder Speicherung niedermolekularer hydrophober Substanzen in verschiedenen
