Anticalin

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3D structure model of an anticalin (ribbon) in complex with digitoxigenin (sticks) 1LNM (Anticalin DIGA16 in complex with digitoxigenin).png
3D structure model of an anticalin (ribbon) in complex with digitoxigenin (sticks)

Anticalin proteins are artificial proteins that are able to bind to antigens, either to proteins or to small molecules. They are not structurally related to antibodies, which makes them a type of antibody mimetic. Instead, they are derived from human lipocalins which are a family of naturally binding proteins. Anticalin proteins are being used in lieu of monoclonal antibodies, but are about eight times smaller with a size of about 180 amino acids and a mass of about 20  kDa.

Contents

The Anticalin technology is exclusively commercialized by Pieris Pharmaceuticals in Freising, Germany. [1] Anticalin is a registered trademark of Pieris.[ citation needed ]

Properties

Anticalin proteins have better tissue penetration than antibodies and are stable at temperatures up to 70 °C. Unlike antibodies, they can be produced in bacterial cells like E. coli in large amounts. [2]

While antibodies can only be directed at macromolecules such as proteins and at small molecules (haptens) only if bound to macromolecules, [3] Anticalin proteins are able to selectively bind to small molecules as well.[ citation needed ]

They were mainly developed at the Technical University of Munich and are currently used as research tools. Diagnostic and therapeutic applications, including the use for targeted drug delivery, are being aimed at. [4] The underlying technology was nominated for the German Future Prize in 2004. [5]

Structure

Characteristic for Anticalin proteins is their barrel structure formed by eight antiparallel β-strands pairwise connected by loops and an attached α-helix. The main structure of Anticalin proteins is identical to wild type lipocalins. Conformational deviations are primarily located in the four loops reaching in the ligand binding site. [2] Mutagenesis of amino acids at the binding site allows for changing the affinity and selectivity.[ citation needed ]

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<span class="mw-page-title-main">Protein</span> Biomolecule consisting of chains of amino acid residues

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<span class="mw-page-title-main">Allosteric regulation</span> Regulation of enzyme activity

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<span class="mw-page-title-main">Binding site</span> Molecule-specific coordinate bonding area in biological systems

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<span class="mw-page-title-main">Lipocalin</span>

The lipocalins are a family of proteins which transport small hydrophobic molecules such as steroids, bilins, retinoids, and lipids, and most lipocalins are also able to bind to complexed iron as well as heme. They share limited regions of sequence homology and a common tertiary structure architecture. This is an eight stranded antiparallel beta barrel with a repeated + 1 topology enclosing an internal ligand binding site.

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<span class="mw-page-title-main">Affitin</span>

Affitins are artificial proteins with the ability to selectively bind antigens. They are structurally derived from the DNA binding protein Sac7d, found in Sulfolobus acidocaldarius, a microorganism belonging to the archaeal domain. By randomizing the amino acids on the binding surface of Sac7d and subjecting the resulting protein library to rounds of ribosome display, the affinity can be directed towards various targets, such as peptides, proteins, viruses, and bacteria.

<span class="mw-page-title-main">Affilin</span> Artificial proteins

Affilins are artificial proteins designed to selectively bind antigens. Affilin proteins are structurally derived from human ubiquitin. Affilin proteins are constructed by modification of surface-exposed amino acids of these proteins and isolated by display techniques such as phage display and screening. They resemble antibodies in their affinity and specificity to antigens but not in structure, which makes them a type of antibody mimetic. Affilin was developed by Scil Proteins GmbH as potential new biopharmaceutical drugs, diagnostics and affinity ligands.

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Molecular Operating Environment (MOE) is a drug discovery software platform that integrates visualization, modeling and simulations, as well as methodology development, in one package. MOE scientific applications are used by biologists, medicinal chemists and computational chemists in pharmaceutical, biotechnology and academic research. MOE runs on Windows, Linux, Unix, and macOS. Main application areas in MOE include structure-based design, fragment-based design, ligand-based design, pharmacophore discovery, medicinal chemistry applications, biologics applications, structural biology and bioinformatics, protein and antibody modeling, molecular modeling and simulations, virtual screening, cheminformatics & QSAR. The Scientific Vector Language (SVL) is the built-in command, scripting and application development language of MOE.

<span class="mw-page-title-main">Optimer ligand</span>

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References

  1. "Pieris Pharmaceuticals, Inc". Pieris Pharmaceuticals, Inc. Retrieved 16 June 2015.
  2. 1 2 Skerra A (June 2008). "Alternative binding proteins: anticalins - harnessing the structural plasticity of the lipocalin ligand pocket to engineer novel binding activities". FEBS J. 275 (11): 2677–83. doi: 10.1111/j.1742-4658.2008.06439.x . PMID   18435758. S2CID   19992238.
  3. Mutschler, Ernst; Schäfer-Korting, Monika (2001). Arzneimittelwirkungen (in German) (8 ed.). Stuttgart: Wissenschaftliche Verlagsgesellschaft. pp. 911f. ISBN   3-8047-1763-2.
  4. Skerra, A (2002). "Anticaline" (PDF). BIOforum (in German). 4/2002. Darmstadt: GIT Verlag: 227–229.[ permanent dead link ]
  5. "Deutscher Zukunftspreis 2004: Anticaline – Biopharmazeutische Wirkstoffe durch Protein-Design" [German Future Prize 2004: Anticalins – Biopharmaceutical agents by protein design] (in German). Stifterverband für die Deutsche Wissenschaft. Archived from the original on 8 December 2010. Retrieved 6 December 2010.