Global Assessment of Drug Target Engagement and Selectivity of Covalent Cysteine-Reactive Inhibitors Using Alkyne-Functionalized Probes.
Activity-based protein profiling
Chemoproteomics
Covalent inhibitors
Cysteine
Target engagement
Journal
Methods in molecular biology (Clifton, N.J.)
ISSN: 1940-6029
Titre abrégé: Methods Mol Biol
Pays: United States
ID NLM: 9214969
Informations de publication
Date de publication:
2023
2023
Historique:
medline:
11
8
2023
pubmed:
10
8
2023
entrez:
9
8
2023
Statut:
ppublish
Résumé
Covalent inhibitors are emerging as a promising therapeutic means for efficient and sustained targeting of key disease-driving proteins. As for classic non-covalent inhibitors, understanding target engagement and selectivity is essential for determining optimal dosing and limiting potential on- or off-target toxicity. Here, we present a complementary activity-based protein profiling (ABPP) strategy for unbiased proteome-wide profiling of cysteine-reactive inhibitors based on two orthogonal approaches. We illustrate the use of clickable alkyne probes for in-gel fluorescence and mass spectrometry studies using a series of therapeutic XPO1 inhibitors as an example.
Identifiants
pubmed: 37558950
doi: 10.1007/978-1-0716-3397-7_14
doi:
Substances chimiques
Cysteine
K848JZ4886
Alkynes
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
191-200Informations de copyright
© 2023. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.
Références
Cook D, Brown D, Alexander R, March R, Morgan P, Satterthwaite G et al (2014) Lessons learned from the fate of AstraZeneca’s drug pipeline: a five-dimensional framework. Nat Rev Drug Discov 13:419–431
doi: 10.1038/nrd4309
pubmed: 24833294
Bunnage ME, Chekler EL, Jones LH (2013) Target validation using chemical probes. Nat Chem Biol 9:195–199
doi: 10.1038/nchembio.1197
pubmed: 23508172
Stefaniak J, Huber KVM (2020) Importance of quantifying drug-target engagement in cells. ACS Med Chem Lett 11:403–406
doi: 10.1021/acsmedchemlett.9b00570
pubmed: 32292539
pmcid: 7153009
Singh J, Petter RC, Baillie TA, Whitty A (2011) The resurgence of covalent drugs. Nat Rev Drug Discov 10:307–317
doi: 10.1038/nrd3410
pubmed: 21455239
Rothweiler EM, Brennan PE, Huber KVM (2022) Covalent fragment-based ligand screening approaches for identification of novel ubiquitin proteasome system modulators. Biol Chem 403:391–402
doi: 10.1515/hsz-2021-0396
pubmed: 35191283
Montano JL, Wang BJ, Volk RF, Warrington SE, Garda VG, Hofmann KL et al (2022) Improved electrophile design for exquisite covalent molecule selectivity. ACS Chem Biol
Jost C, Nitsche C, Scholz T, Roux L, Klein CD (2014) Promiscuity and selectivity in covalent enzyme inhibition: a systematic study of electrophilic fragments. J Med Chem 57:7590–7599
doi: 10.1021/jm5006918
pubmed: 25148591
Vinogradova EV, Zhang X, Remillard D, Lazar DC, Suciu RM, Wang Y et al (2020) An activity-guided map of electrophile-cysteine interactions in primary human T cells. Cell 182:1009–26.e29
doi: 10.1016/j.cell.2020.07.001
pubmed: 32730809
pmcid: 7775622
Robers MB, Friedman-Ohana R, Huber KVM, Kilpatrick L, Vasta JD, Berger BT et al (2020) Quantifying target occupancy of small molecules within living cells. Annu Rev Biochem 89:557–581
doi: 10.1146/annurev-biochem-011420-092302
pubmed: 32208767
Ward JA, Pinto-Fernandez A, Cornelissen L, Bonham S, Diaz-Saez L, Riant O et al (2020) Re-evaluating the mechanism of action of alpha, beta-unsaturated carbonyl DUB Inhibitors b-AP15 and VLX1570: a paradigmatic example of unspecific protein cross-linking with Michael acceptor motif-containing drugs. J Med Chem 63:3756–3762
doi: 10.1021/acs.jmedchem.0c00144
pubmed: 32109059
pmcid: 7152998
Ward JA, McLellan L, Stockley M, Gibson KR, Whitlock GA, Knights C et al (2016) Quantitative chemical proteomic profiling of ubiquitin specific proteases in intact cancer cells. ACS Chem Biol 11:3268–3272
doi: 10.1021/acschembio.6b00766
pubmed: 27779380
Weerapana E, Speers AE, Cravatt BF (2007) Tandem orthogonal proteolysis-activity-based protein profiling (TOP-ABPP)—a general method for mapping sites of probe modification in proteomes. Nat Protoc 2:1414–1425
doi: 10.1038/nprot.2007.194
pubmed: 17545978
Weerapana E, Wang C, Simon GM, Richter F, Khare S, Dillon MBD et al (2010) Quantitative reactivity profiling predicts functional cysteines in proteomes. Nature 468:790–795
doi: 10.1038/nature09472
pubmed: 21085121
pmcid: 3058684
Zanon PRA, Yu F, Musacchio PZ, Lewald L, Zollo M, Krauskopf K et al (2021) Profiling the proteome-wide selectivity of diverse electrophiles. ChemRXiv
Hahm HS, Toroitich EK, Borne AL, Brulet JW, Libby AH, Yuan K et al (2019) Global targeting of functional tyrosines using sulfur-triazole exchange chemistry. Nat Chem Biol
Chung CY-S, Shin HR, Berdan CA, Ford B, Ward CC, Olzmann JA et al (2019) Covalent targeting of the vacuolar H+-ATPase activates autophagy via mTORC1 inhibition. Nat Chem Biol 15:776–785
doi: 10.1038/s41589-019-0308-4
pubmed: 31285595
Apel C, Kasper MA, Stieger CE, Hackenberger CPR, Christmann M (2019) Protein modification of lysine with 2-(2-Styrylcyclopropyl)ethanal. Org Lett 21:10043–10047
doi: 10.1021/acs.orglett.9b03982
pubmed: 31825637
Ward CC, Kleinman JI, Nomura DK (2017) NHS-esters as versatile reactivity-based probes for mapping proteome-wide Ligandable hotspots. ACS Chem Biol 12:1478–1483
doi: 10.1021/acschembio.7b00125
pubmed: 28445029
pmcid: 7771572
Lin S, Yang X, Jia S, Weeks AM, Hornsby M, Lee PS et al (2017) Redox-based reagents for chemoselective methionine bioconjugation. Science 355:597–602
doi: 10.1126/science.aal3316
pubmed: 28183972
pmcid: 5827972
Shannon DA, Gu C, McLaughlin CJ, Kaiser M, van der Hoorn RA, Weerapana E (2012) Sulfonyl fluoride analogues as activity-based probes for serine proteases. Chembiochem 13:2327–2330
doi: 10.1002/cbic.201200531
pubmed: 23008217
Wang C, Abegg D, Dwyer BG, Adibekian A (2019) Discovery and evaluation of new activity-based probes for serine hydrolases. Chembiochem 20:2212–2216
doi: 10.1002/cbic.201900126
pubmed: 30968522
Scheer S, Ackloo S, Medina TS, Schapira M, Li F, Ward JA et al (2019) A chemical biology toolbox to study protein methyltransferases and epigenetic signaling. Nat Commun 10:19
doi: 10.1038/s41467-018-07905-4
pubmed: 30604761
pmcid: 6318333