Protein-Templated Fragment Ligations-From Molecular Recognition to Drug Discovery

Overview

Journal Angew Chem Int Ed Engl

Specialty Chemistry

Date 2017 Jan 25

PMID 28117936

Citations 27

Authors

Mike Jaegle

Ee Lin Wong

Carolin Tauber

Eric Nawrotzky

Christoph Arkona

Jorg Rademann

Affiliations

Soon will be listed here.

Abstract

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.

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