Optical control of targeted protein degradation

Martin Reynders; Dirk Trauner

doi:10.1016/j.chembiol.2021.05.010

Optical control of targeted protein degradation

Cell Chem Biol. 2021 Jul 15;28(7):969-986. doi: 10.1016/j.chembiol.2021.05.010. Epub 2021 Jun 10.

Authors

Martin Reynders¹, Dirk Trauner²

Affiliations

¹ Department of Chemistry, New York University, New York, NY 10003, USA; Department of Chemistry, Ludwig Maximilians University of Munich, 81377 Munich, Germany.
² Department of Chemistry, New York University, New York, NY 10003, USA; Perlmutter Cancer Center, New York University School of Medicine, New York, NY 10016, USA; NYU Neuroscience Institute, New York University School of Medicine, New York, NY 10016, USA. Electronic address: [email protected].

PMID: 34115971
DOI: 10.1016/j.chembiol.2021.05.010

Abstract

Molecular glues and proteolysis targeting chimeras (PROTACs) have emerged as small-molecule tools that selectively induce the degradation of a chosen protein and have shown therapeutic promise. Recently, several approaches employing light as an additional stimulus to control induced protein degradation have been reported. Here, we analyze the principles guiding the design of such systems, provide a survey of the literature published to date, and discuss opportunities for further development. Light-responsive degraders enable the precise temporal and spatial control of protein levels, making them useful research tools but also potential candidates for human precision medicine.

Keywords: PHOTAC; PROTAC; chemical optogenetics; photoactivation; photocleavable protecting group; photopharmacology; photoswitch.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Humans
Precision Medicine
Proteins / antagonists & inhibitors*
Proteins / metabolism
Proteolysis / drug effects
Small Molecule Libraries / chemistry
Small Molecule Libraries / pharmacology*

Substances

Proteins
Small Molecule Libraries