Examining targeted protein degradation from physiological and analytical perspectives: Enabling translation between cells and subjects.

Title

Examining targeted protein degradation from physiological and analytical perspectives: Enabling translation between cells and subjects.

Creator

Daurio NA;Zhou H;Chen Y;Sheth PR;Imbriglio JE;McLaren DG;Tawa P;Rachdaoui N;Previs MJ;Kasumov T;O'Neil J;Previs SF

Publisher

ACS Chemical Biology

Date

2020
2020-09-30

Description

The ability to target specific proteins for degradation may open a new door toward developing therapeutics. Although effort in chemistry is essential for advancing this modality, i.e., one needs to generate proteolysis targeting chimeras (bifunctional molecules, also referred to as PROTACS) or "molecular glues" to accelerate protein degradation, we suspect that investigations could also benefit by directing attention toward physiological regulation surrounding protein homeostasis, including the methods that can be used to examine changes in protein kinetics. This perspective will first consider some metabolic scenarios that might be of importance when one aims to change protein abundance by increasing protein degradation. Specifically, could protein turnover impact the apparent outcome? We will then outline how to study protein dynamics by coupling stable isotope tracer methods with mass spectrometry-based detection; since the experimental conditions could have a dramatic effect on protein turnover, special attention is directed toward the application of methods for quantifying protein kinetics using in vitro and in vivo models. Our goal is to present key concepts that should enable mechanistically informed studies which test targeted protein degradation strategies.

Rights

Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).

Format

journalArticle

Search for Full-text

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ISSN

1554-8937

NEOMED College

NEOMED College of Pharmacy

NEOMED Department

Department of Pharmaceutical Sciences

Update Year & Number

September 2020 List

Citation

Daurio NA;Zhou H;Chen Y;Sheth PR;Imbriglio JE;McLaren DG;Tawa P;Rachdaoui N;Previs MJ;Kasumov T;O'Neil J;Previs SF, “Examining targeted protein degradation from physiological and analytical perspectives: Enabling translation between cells and subjects.,” NEOMED Bibliography Database, accessed June 23, 2021, https://neomed.omeka.net/items/show/11276.

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