Intracellular Protein-Drug Interactions Probed by Direct Mass Spectrometry of Cell Lysates.
analytical methods
drug discovery
drug screening
mass spectrometry
protein analysis
Journal
Angewandte Chemie (International ed. in English)
ISSN: 1521-3773
Titre abrégé: Angew Chem Int Ed Engl
Pays: Germany
ID NLM: 0370543
Informations de publication
Date de publication:
01 09 2021
01 09 2021
Historique:
revised:
23
05
2021
received:
11
04
2021
pubmed:
9
6
2021
medline:
4
11
2021
entrez:
8
6
2021
Statut:
ppublish
Résumé
Understanding protein-ligand interactions in a cellular context is an important goal in molecular biology and biochemistry, and particularly for drug development. Investigators must demonstrate that drugs penetrate cells and specifically bind their targets. Towards that end, we present a native mass spectrometry (MS)-based method for analyzing drug uptake and target engagement in eukaryotic cells. This method is based on our previously introduced direct-MS method for rapid analysis of proteins directly from crude samples. Here, direct-MS enables label-free studies of protein-drug binding in human cells and is used to determine binding affinities of lead compounds in crude samples. We anticipate that this method will enable the application of native MS to a range of problems where cellular context is important, including protein-protein interactions, drug uptake and binding, and characterization of therapeutic proteins.
Identifiants
pubmed: 34101963
doi: 10.1002/anie.202104947
pmc: PMC8457057
doi:
Substances chimiques
Ligands
0
Pharmaceutical Preparations
0
Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
19637-19642Informations de copyright
© 2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.
Références
Nat Chem Biol. 2013 May;9(5):297-9
pubmed: 23455544
Nat Rev Drug Discov. 2012 Apr 30;11(5):355-65
pubmed: 22543468
Alzheimers Dement (N Y). 2017 Nov 11;3(4):651-657
pubmed: 29255791
Commun Biol. 2018 Dec 3;1:213
pubmed: 30534605
Proc Natl Acad Sci U S A. 2010 Jul 20;107(29):13075-80
pubmed: 20615965
ACS Omega. 2017 Aug 09;2(8):4398-4410
pubmed: 31457731
Nat Protoc. 2016 Jun;11(6):1101-11
pubmed: 27196722
FEBS Lett. 1995 Feb 27;360(2):111-4
pubmed: 7875313
Curr Protoc Immunol. 2015 Nov 02;111:A3.B.1-A3.B.3
pubmed: 26529666
J Mass Spectrom. 2008 May;43(5):600-8
pubmed: 18074334
Science. 2014 Oct 3;346(6205):1255784
pubmed: 25278616
ACS Chem Neurosci. 2020 Jan 15;11(2):184-190
pubmed: 31820923
Nat Protoc. 2020 Feb;15(2):236-265
pubmed: 31942081
Leukemia. 2021 Feb;35(2):312-332
pubmed: 33122850
Anal Chem. 2020 Jul 21;92(14):9997-10006
pubmed: 32551584
EMBO J. 2016 Dec 15;35(24):2634-2657
pubmed: 27797822
ACS Chem Biol. 2014 Jan 17;9(1):218-26
pubmed: 24128068
J Mol Biol. 2020 Nov 20;432(23):5995-6002
pubmed: 33058881
Anal Chem. 2013 Mar 5;85(5):2724-30
pubmed: 23347283
Acta Crystallogr D Biol Crystallogr. 2006 Oct;62(Pt 10):1243-50
pubmed: 17001101
Nat Biotechnol. 2004 Nov;22(11):1393-8
pubmed: 15529164
Science. 2013 May 31;340(6136):1059-60
pubmed: 23723227
Biochim Biophys Acta. 2006 Nov-Dec;1762(11-12):1025-37
pubmed: 16814528
Biochem Biophys Res Commun. 2014 Mar 21;445(4):683-93
pubmed: 24556311
J Am Soc Mass Spectrom. 2005 Jul;16(7):1031-8
pubmed: 15914025
Angew Chem Int Ed Engl. 2021 Sep 1;60(36):19637-19642
pubmed: 34101963
Sci Rep. 2013 Nov 20;3:3275
pubmed: 24253732
J Am Soc Mass Spectrom. 2012 Mar;23(3):431-41
pubmed: 22270873
Anal Chem. 2017 Apr 18;89(8):4398-4404
pubmed: 28345863
Expert Rev Proteomics. 2006 Dec;3(6):611-9
pubmed: 17181475
Curr Opin Chem Biol. 2004 Feb;8(1):60-5
pubmed: 15036158
J Am Chem Soc. 2021 Apr 7;143(13):4979-4992
pubmed: 33761747
Curr Opin Struct Biol. 2015 Oct;34:7-16
pubmed: 26005781