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Anticalin® proteins: from bench to bedside.

Friedrich-Christian Deuschle1, Elena Ilyukhina1, Arne Skerra1

  • 1Chair of Biological Chemistry, School of Life Sciences, Technical University of Munich, Freising, Germany.

Expert Opinion on Biological Therapy
|October 19, 2020
PubMed
Summary

Anticalin proteins, engineered lipocalins, offer a novel biopharmaceutical class. They demonstrate high specificity and affinity for diverse targets, advancing drug development for oncology, metabolic diseases, and more.

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Structural Basis of the Light-Switchable Interaction between an Azobenzene Side Chain in a Biosynthetic Protein and α-Cyclodextrin.

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Design of a ligand-dependent fluorescent biosensor, based on an engineered lipocalin (anticalin), for the sensitive detection of the Alzheimer β-amyloid peptide.

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Area of Science:

  • Biopharmaceutical Engineering
  • Protein Engineering
  • Drug Discovery

Background:

  • Anticalins are engineered lipocalins with a unique β-barrel structure and adaptable binding pocket.
  • Lipocalins naturally bind small molecules, but engineering expands their specificity to peptides and proteins.

Purpose of the Study:

  • To review the engineering principles and development status of Anticalin proteins.
  • To highlight Anticalin-based drug candidates in preclinical and clinical development.
  • To discuss Anticalins as a potential alternative to antibodies.

Main Methods:

  • Combinatorial protein design and directed evolution are employed to engineer Anticalins.
  • Molecular selection techniques expand lipocalin ligand specificities.
Keywords:
Binding proteinbiopharmaceuticallipocalinprotein designprotein scaffold

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  • Structural analyses validate Anticalin-target interactions.

    • Main Results:

    • Anticalins exhibit high target affinity and specificity.
    • Anticalin lead candidates are in development for oncology, metabolic, respiratory diseases, intoxications, and infections.
    • Structural studies confirm the biomolecular concept of Anticalin engineering.

    Conclusions:

    • Anticalins represent a novel class of clinical-stage biopharmaceuticals with broad therapeutic potential.
    • They offer promising features as next-generation biologics, potentially superior to antibodies.
    • Anticalin technology is validated and progressing through drug development pipelines.