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  Rational design of an DNA-scaffolded high-affinity binder for langerin

Bachem, G., Wamhoff, E.-C., Silberreis, K., Kim, D., Baukmann, H., Fuchsberger, F. F., et al. (2020). Rational design of an DNA-scaffolded high-affinity binder for langerin. Angewandte Chemie International Edition, 59(47), 21016-21022. doi:10.1002/anie.202006880.

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 Creators:
Bachem, Gunnar, Author
Wamhoff, Eike-Christian1, Author              
Silberreis, Kim, Author
Kim, Dongyoon1, Author              
Baukmann, Hannes1, Author              
Fuchsberger, Felix F.1, Author              
Dernedde, Jens, Author
Rademacher, Christoph1, Author              
Seitz, Oliver, Author
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1Christoph Rademacher, Biomolekulare Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society, ou_1863300              

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Free keywords: Lectins, carbohyhydrate recognition, peptide nucleic acid, multivalent interactions, DNA nanotechnology
 Abstract: Binders of Langerin could target vaccines to Langerhans cells for improved therapeutic effect. As Langerin has only low affinity for monovalent glycan ligands, highly multivalent presentation has previously been key for targeting. Aiming to reduce the amount of ligands required, we rationally designed molecularly defined high affinity binders based on the precise display of glycomimetic ligands (Glc2NTs) on DNA-PNA scaffolds. Rather than mimicking Langerin?s homotrimeric structure with a C3-symmetrical scaffold, we devised a strategy to improve readily accessible, easy to design bivalent binders. The method considers the requirements for bridging sugar binding sites and statistical rebinding as a means to both strengthen the interactions at single binding sites and amplify the avidity enhancement provided by chelation. The method enabled a 1150-fold net improvement over the affinity of the free ligand and provided a nanomolar binder (IC50 = 300 nM) for specific internalization by Langerin expressing cells.

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Language(s): eng - English
 Dates: 2020-08-042020
 Publication Status: Published in print
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Title: Angewandte Chemie International Edition
  Abbreviation : Angew. Chem., Int. Ed.
Source Genre: Journal
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Publ. Info: Weinheim : Wiley-VCH
Pages: - Volume / Issue: 59 (47) Sequence Number: - Start / End Page: 21016 - 21022 Identifier: ISSN: 1433-7851

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Title: Angewandte Chemie
  Abbreviation : Angew. Chem.
Source Genre: Journal
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Publ. Info: Weinheim : Wiley-VCH
Pages: - Volume / Issue: 132 (47) Sequence Number: - Start / End Page: 21202 - 21208 Identifier: ISSN: 0044-8249