Emerging Methods in Chemoproteomics with Relevance to Drug Discovery.
A powerful interplay exists between the recognition of gene families, sensitive techniques in proteomics, and the interrogation of protein function using chemical probes. The most prominent methods, such as affinity capture, activity-based protein profiling and photoaffinity labeling, are extensively reviewed in the literature. Here we briefly review additional methods developed in the past 15 years. These include "stability proteomics" methods such as proteomically analyzed cellular thermal shift assays and the use of chemical oxidation as a probe of structure, the use of multiple bead-linked kinase inhibitors to analyze inhibitor specificities, and advances in the use of proteolysis-targeting chimeras for selective protein elimination.
Structural Biology and Biophysics, Pfizer Worldwide Research, Groton, CT, 06340, USA.
Chuong
C
Nguyen
Structural Biology and Biophysics, Pfizer Worldwide Research, Groton, CT, 06340, USA.
Graham M
GM
West
Structural Biology and Biophysics, Pfizer Worldwide Research, Groton, CT, 06340, USA. kieran.f.geoghegan@pfizer.com.
Kieran F
KF
Geoghegan
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001681:Biological Assay; D055808:Drug Discovery / Q000379:methods*; D015870:Gene Expression; D006801:Humans; D020014:K562 Cells; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D010084:Oxidation-Reduction; D011489:Protein Denaturation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011494:Protein Kinases / Q000235:genetics* / Q000378:metabolism; D055550:Protein Stability / Q000187:drug effects; D040901:Proteomics / Q000379:methods*; D013816:Thermodynamics
D000970:Antineoplastic Agents; D009363:Neoplasm Proteins; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases
CETSA; Chemoproteomics; DARTS; Kinobeads; LiP-SRM; PROTAC; Proteomics; SPROX