Genetic manipulation and targeted protein degradation in mammalian systems: practical considerations, tips and tricks for discovery research.
Sign Up to like & getrecommendations! Published in 2023 at "FEBS open bio"
DOI: 10.1002/2211-5463.13581
Abstract: Gaining a mechanistic understanding of the molecular pathways underpinning cellular and organismal physiology invariably relies on perturbation of an experimental system to infer causality. This can be achieved either by genetic manipulation or by pharmacological… read more here.
Keywords: mammalian systems; genetic manipulation; targeted protein; manipulation ... See more keywords
Multifaceted targeted protein degradation systems for different cellular compartments
Sign Up to like & getrecommendations! Published in 2022 at "BioEssays"
DOI: 10.1002/bies.202200008
Abstract: Selective protein degradation maintains cellular homeostasis, but this process is disrupted in many diseases. Targeted protein degradation (TPD) approaches, built upon existing cellular mechanisms, are promising methods for therapeutically regulating protein levels. Here, we review… read more here.
Keywords: cellular compartments; targeting chimeras; protein degradation; targeted protein ... See more keywords
Repurposing a DNA‐Repair Enzyme for Targeted Protein Degradation
Sign Up to like & getrecommendations! Published in 2022 at "ChemBioChem"
DOI: 10.1002/cbic.202200053
Abstract: Herein we present the exploration of the utility of DNA demethylase enzymes for targeted protein degradation. Novel benzylguanine substrates are characterized for their ability to control protein degradation in cells. Our data demonstrate the utility… read more here.
Keywords: dna repair; repurposing dna; targeted protein; protein degradation ... See more keywords
Construction and Functionalization of a Clathrin Assembly for a Targeted Protein Delivery.
Sign Up to like & getrecommendations! Published in 2022 at "Small"
DOI: 10.1002/smll.202204620
Abstract: Protein assemblies have drawn much attention as platforms for biomedical applications, including gene/drug delivery and vaccine, due to biocompatibility and functional diversity. Here, the construction and functionalization of a protein assembly composed of human clathrin… read more here.
Keywords: construction functionalization; targeted protein; clathrin assembly; clathrin ... See more keywords
Targeted Protein Degradation Technology and Nanomedicine: Powerful Allies against Cancer.
Sign Up to like & getrecommendations! Published in 2023 at "Small"
DOI: 10.1002/smll.202207778
Abstract: Targeted protein degradation (TPD) is an emerging therapeutic strategy with the potential of targeting undruggable pathogenic proteins. After the first proof-of-concept proteolysis-targeting chimeric (PROTAC) molecule was reported, the TPD field has entered a new era. In… read more here.
Keywords: tpd; targeted protein; degradation technology; protein degradation ... See more keywords
Taking the Brakes Off Targeted Protein Degradation.
Sign Up to like & getrecommendations! Published in 2020 at "Cell chemical biology"
DOI: 10.1016/j.chembiol.2019.12.010
Abstract: PCSK9 heightens LDL cholesterol levels by chaperoning the liver LDL receptor to lysosomes for degradation. In this issue of Cell Chemical Biology, Petrilli et al. (2020) identify novel PCSK9 ligands and convert them into a proof-of-concept… read more here.
Keywords: taking brakes; brakes targeted; protein degradation; biology ... See more keywords
Optical control of targeted protein degradation.
Sign Up to like & getrecommendations! Published in 2021 at "Cell chemical biology"
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… read more here.
Keywords: degradation; control targeted; control; protein degradation ... See more keywords
Fundamental aspects of DMPK optimization of targeted protein degraders.
Sign Up to like & getrecommendations! Published in 2020 at "Drug discovery today"
DOI: 10.1016/j.drudis.2020.03.012
Abstract: Targeted protein degraders are an emerging modality. Their properties fall outside the traditional small-molecule property space and are in the 'beyond rule of 5' space. Consequently, drug discovery programs focused on developing orally available degraders… read more here.
Keywords: aspects dmpk; protein degraders; optimization; targeted protein ... See more keywords
Harnessing the Power of Proteolysis for Targeted Protein Inactivation.
Sign Up to like & getrecommendations! Published in 2020 at "Molecular cell"
DOI: 10.1016/j.molcel.2020.01.010
Abstract: Two decades into the twenty-first century, a confluence of breakthrough technologies wielded at the molecular level is presenting biologists with unique opportunities to unravel the complexities of the cellular world. CRISPR/Cas9 allows gene knock-outs, knock-ins,… read more here.
Keywords: harnessing power; protein inactivation; power proteolysis; proteolysis targeted ... See more keywords
Critical Assessment of Targeted Protein Degradation as a Research Tool and Pharmacological Modality.
Sign Up to like & getrecommendations! Published in 2020 at "Trends in pharmacological sciences"
DOI: 10.1016/j.tips.2020.02.006
Abstract: Small molecules continue to dominate drug discovery because of their ease of use, lower cost of manufacturing, and access to intracellular targets. However, despite these advantages, small molecules are more likely to fail in clinical… read more here.
Keywords: protein degradation; targeted protein; critical assessment; pharmacological modality ... See more keywords
Molecular Glues: The Adhesive Connecting Targeted Protein Degradation to the Clinic
Sign Up to like & getrecommendations! Published in 2022 at "Biochemistry"
DOI: 10.1021/acs.biochem.2c00245
Abstract: Targeted protein degradation is a rapidly exploding drug discovery strategy that uses small molecules to recruit disease-causing proteins for rapid destruction mainly via the ubiquitin–proteasome pathway. It shows great potential for treating diseases such as… read more here.
Keywords: drug discovery; targeted protein; protein degradation; molecular glues ... See more keywords