• Medientyp: E-Book
  • Titel: Rational Structure-Based Rescaffolding Approach to De Novo Design of Interleukin 10 (IL-10) Receptor-1 Mimetics
  • Beteiligte: Ruiz-Gómez, Gloria [Autor/In]; Hawkins, John C. [Autor/In]; Philipp, Jenny [Autor/In]; Künze, Georg [Autor/In]; Wodtke, Robert [Autor/In]; Löser, Reik [Autor/In]; Fahmy, Karim Y. [Autor/In]; Pisabarro, M. Teresa [Autor/In]
  • Erschienen: Lawrence, Kan. : Public Library of Science, 2017
  • Umfang: 1 Online-Ressource
  • Sprache: Englisch
  • RVK-Notation: XA 10000 : Medizinische Zeitschriften
  • Beschreibung: 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.