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Protein‐Templated Fragment Ligations—From Molecular Recognition to Drug Discovery
Author(s) -
Jaegle Mike,
Wong Ee Lin,
Tauber Carolin,
Nawrotzky Eric,
Arkona Christoph,
Rademann Jörg
Publication year - 2017
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201610372
Subject(s) - drug discovery , protein ligand , chemistry , combinatorial chemistry , fragment (logic) , native chemical ligation , small molecule , ligand (biochemistry) , ligation , chemical biology , target protein , chemical ligation , computational biology , molecule , chemical synthesis , stereochemistry , biochemistry , in vitro , receptor , biology , peptide , organic chemistry , microbiology and biotechnology , computer science , gene , programming language
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.