- AutorIn
- Dr. Gloria Ruiz-Gómez
- Dr. John C. Hawkins
- Jenny Philipp
- M. Sc. Georg Künze
- Robert Wodtke
- Dr. Reik Löser
- Prof. Dr. habil. Karim Fahmy
- Dr. M. Teresa Pisabarro
- Titel
- Rational Structure-Based Rescaffolding Approach to De Novo Design of Interleukin 10 (IL-10) Receptor-1 Mimetics
- Zitierfähige Url:
- https://nbn-resolving.org/urn:nbn:de:bsz:14-qucosa-215877
- Quellenangabe
- PLOS ONE (2016), 11(4). ISSN 1932-6203. DOI: 10.1371/journal.pone.0154046
- Erstveröffentlichung
- 2016
- Abstract (EN)
- Tackling protein interfaces with small molecules capable of modulating protein-protein interactions remains a challenge in structure-based ligand design. Particularly arduous are cases in which the epitopes involved in molecular recognition have a non-structured and discontinuous nature. Here, the basic strategy of translating continuous binding epitopes into mimetic scaffolds cannot be applied, and other innovative approaches are therefore required. We present a structure-based rational approach involving the use of a regular expression syntax inspired in the well established PROSITE to define minimal descriptors of geometric and functional constraints signifying relevant functionalities for recognition in protein interfaces of non-continuous and unstructured nature. These descriptors feed a search engine that explores the currently available three-dimensional chemical space of the Protein Data Bank (PDB) in order to identify in a straightforward manner regular architectures containing the desired functionalities, which could be used as templates to guide the rational design of small natural-like scaffolds mimicking the targeted recognition site. The application of this rescaffolding strategy to the discovery of natural scaffolds incorporating a selection of functionalities of interleukin-10 receptor-1 (IL-10R1), which are relevant for its interaction with interleukin-10 (IL-10) has resulted in the de novo design of a new class of potent IL-10 peptidomimetic ligands.
- Andere Ausgabe
- DOI: 10.1371/journal.pone.0154046
- Link zum Artikel, der zuerst in der Zeitschrift 'PLOS ONE' erschienen ist.
Link: http://dx.doi.org/10.1371/journal.pone.0154046 - Freie Schlagwörter (DE)
- Protein-Protein-Interaktionen (PPIs), Protein-Interfaces, natürliche Gerüste, Nachahmung, TU Dresden, Publikationsfonds
- Freie Schlagwörter (EN)
- Protein-protein interactions (PPIs), protein interfaces, natural-like scaffolds, mimicking, TU Dresden, Publishing Fund
- Klassifikation (DDC)
- 610
- Klassifikation (RVK)
- XA 10000
- Verlag
- Public Library of Science, Lawrence, Kan.
- URN Qucosa
- urn:nbn:de:bsz:14-qucosa-215877
- Veröffentlichungsdatum Qucosa
- 06.01.2017
- Dokumenttyp
- Artikel
- Sprache des Dokumentes
- Englisch
- Lizenz / Rechtehinweis
- CC BY 4.0