Protein‐Templated Fragment Ligations—From Molecular Recognition to Drug Discovery
Protein‐templated fragment ligation is a novel concept to support drug discovery and can help to improve the efficacy of protein ligands. Protein‐templated fragment ligations are chemical reactions between small molecules (“fragments”) utilizing a protein's surface as a reaction vessel to catal...
Gespeichert in:
Veröffentlicht in: | Angewandte Chemie International Edition 2017-06, Vol.56 (26), p.7358-7378 |
---|---|
Hauptverfasser: | , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
Zusammenfassung: | Protein‐templated fragment ligation is a novel concept to support drug discovery and can help to improve the efficacy of protein ligands. Protein‐templated fragment ligations are chemical reactions between small molecules (“fragments”) utilizing a protein's surface as a reaction vessel to catalyze the formation of a protein ligand with increased binding affinity. The approach exploits the molecular recognition of reactive small‐molecule fragments by proteins both for ligand assembly and for the identification of bioactive fragment combinations. In this way, chemical synthesis and bioassay are integrated in one single step. This Review discusses the biophysical basis of reversible and irreversible fragment ligations and gives an overview of the available methods to detect protein‐templated ligation products. The chemical scope and recent applications as well as future potential of the concept in drug discovery are reviewed.
Can drugs be discovered by using proteins as reactors? Proteins have been found to induce reversible and irreversible ligations of protein‐binding fragments. This Review considers the chemistry and the biophysics of such reactions. The potential of template‐catalyzed reactions in drug discovery and as an alternative mode of drug action is discussed. |
---|---|
ISSN: | 1433-7851 1521-3773 1521-3773 |
DOI: | 10.1002/anie.201610372 |