Bifunctional chemical probes inducing protein-protein interactions

Copyright © 2019 Elsevier Ltd. All rights reserved..

Inducing biomolecular interactions with synthetic molecules to impact biological function is a concept of enormous appeal. Recent years have seen a resurgence of interest in designing bispecific molecules that serve as bridging agents to bring proteins together. Pioneering structural and biophysical investigation of ternary complexes formed by mono-functional and bifunctional ligands highlights that proximity-induced stabilization or de novo formation of protein-protein interactions is a common feature of their molecular recognition. In this review, we illustrate these concepts and advances with representative case studies, and highlight progress over the past three years, with particular focus on recruitment to E3 ubiquitin ligases by 'molecular glues' and chimeric dimerizers (PROTACs) for targeted protein degradation. This approach promises to significantly expand the range of tractable targets for chemical biology and therapeutic intervention.

Medienart:

E-Artikel

Erscheinungsjahr:

2019

Erschienen:

2019

Enthalten in:

Zur Gesamtaufnahme - volume:52

Enthalten in:

Current opinion in chemical biology - 52(2019) vom: 15. Okt., Seite 145-156

Sprache:

Englisch

Beteiligte Personen:

Maniaci, Chiara [VerfasserIn]
Ciulli, Alessio [VerfasserIn]

Links:

Volltext

Themen:

EC 2.3.2.27
Journal Article
Ligands
Molecular Probes
Proteins
Research Support, Non-U.S. Gov't
Review
Ubiquitin-Protein Ligases

Anmerkungen:

Date Completed 02.04.2020

Date Revised 02.04.2020

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1016/j.cbpa.2019.07.003

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM300298730