Anticalins: exploiting a non-Ig scaffold with hypervariable loops for the engineering of binding proteins
A Richter1, E Eggenstein1, A Skerra1
1Munich Center for integrated Protein Science (CiPS-M) and Lehrstuhl für Biologische Chemie, Technische Universität München, Emil-Erlenmeyer-Forum 5, 85350 Freising-Weihenstephan, Germany.
FEBS Letters
|November 19, 2013
Summary
Researchers engineered Anticalins, novel binding proteins derived from human lipocalins, with high affinity for various targets. These engineered proteins show promise as a new class of biopharmaceuticals for medical applications.
Area of Science:
- Biotechnology
- Protein Engineering
- Immunology
Background:
- Antibodies are natural binding proteins, serving as a model for protein engineering.
- Lipocalins are a protein family with ligand-binding functions, featuring a conserved framework and variable loops.
- This structure makes lipocalins an ideal platform for engineering novel binding reagents.
Purpose of the Study:
- To engineer novel binding proteins, termed Anticalins, using the lipocalin platform.
- To develop Anticalins with high specificity and affinity for diverse targets relevant to research and medicine.
Main Methods:
- Utilizing recombinant/synthetic DNA technology.
- Employing combinatorial library selection methods.
- Engineering Anticalins derived from human lipocalins.
Main Results:
- Successfully generated Anticalins with picomolar affinities.
- Developed Anticalins targeting small molecules, peptides, protein signaling molecules, and cell surface receptors.
- Anticalins derived from human lipocalins have advanced to clinical trials.
Conclusions:
- Anticalins represent a versatile platform for creating targeted binding proteins.
- Their small size and single-polypeptide structure facilitate fusion protein construction.
- Anticalins hold significant potential as a new class of biopharmaceuticals.
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