A simple method for developing lysine targeted covalent protein reagents.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
01 Dec 2023
01 Dec 2023
Historique:
received:
13
04
2023
accepted:
16
10
2023
medline:
4
12
2023
pubmed:
2
12
2023
entrez:
1
12
2023
Statut:
epublish
Résumé
Peptide-based covalent probes can target shallow protein surfaces not typically addressable using small molecules, yet there is a need for versatile approaches to convert native peptide sequences into covalent binders that can target a broad range of residues. Here we report protein-based thio-methacrylate esters-electrophiles that can be installed easily on unprotected peptides and proteins via cysteine side chains, and react efficiently and selectively with cysteine and lysine side chains on the target. Methacrylate phosphopeptides derived from 14-3-3-binding proteins irreversibly label 14-3-3σ via either lysine or cysteine residues, depending on the position of the electrophile. Methacrylate peptides targeting a conserved lysine residue exhibit pan-isoform binding of 14-3-3 proteins both in lysates and in extracellular media. Finally, we apply this approach to develop protein-based covalent binders. A methacrylate-modified variant of the colicin E9 immunity protein irreversibly binds to the E9 DNAse, resulting in significantly higher thermal stability relative to the non-covalent complex. Our approach offers a simple and versatile route to convert peptides and proteins into potent covalent binders.
Identifiants
pubmed: 38040731
doi: 10.1038/s41467-023-42632-5
pii: 10.1038/s41467-023-42632-5
pmc: PMC10692228
doi:
Substances chimiques
Lysine
K3Z4F929H6
Indicators and Reagents
0
Cysteine
K848JZ4886
Proteins
0
Peptides
0
Methacrylates
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
7933Subventions
Organisme : Israel Science Foundation (ISF)
ID : 2462/19
Informations de copyright
© 2023. The Author(s).
Références
Nat Commun. 2022 Oct 13;13(1):6038
pubmed: 36229616
Clin Cancer Res. 2022 Sep 1;28(17):3729-3741
pubmed: 35792882
Acta Crystallogr D Struct Biol. 2018 Jun 1;74(Pt 6):506-518
pubmed: 29872002
Nat Methods. 2020 Sep;17(9):869-870
pubmed: 32669682
J Am Chem Soc. 2019 May 8;141(18):7294-7301
pubmed: 31017395
J Med Chem. 2020 Jul 9;63(13):6679-6693
pubmed: 32250617
Nat Methods. 2017 May;14(5):513-520
pubmed: 28394336
ACS Chem Biol. 2022 Nov 18;17(11):3131-3139
pubmed: 36279267
ACS Med Chem Lett. 2011 Feb 10;2(2):91-96
pubmed: 21666860
J Mol Biol. 2000 Sep 1;301(5):1163-78
pubmed: 10966813
J Pept Sci. 2023 Jan;29(1):e3457
pubmed: 36239115
J Am Chem Soc. 2021 Jun 9;143(22):8454-8464
pubmed: 34047554
Acta Crystallogr D Biol Crystallogr. 2011 Apr;67(Pt 4):235-42
pubmed: 21460441
Cell Chem Biol. 2022 May 19;29(5):897-909.e7
pubmed: 34599874
J Med Chem. 2021 Mar 11;64(5):2608-2621
pubmed: 33600174
ACS Chem Biol. 2016 Jan 15;11(1):149-58
pubmed: 26524220
Cell. 2020 Jul 9;182(1):85-97.e16
pubmed: 32579975
Chem Sci. 2021 Sep 9;12(40):13321-13330
pubmed: 34777751
J Am Chem Soc. 2016 Jun 15;138(23):7353-64
pubmed: 27191344
Nat Biotechnol. 2021 Apr;39(4):490-498
pubmed: 33199876
J Am Chem Soc. 2021 Jul 14;143(27):10341-10351
pubmed: 34213894
PLoS One. 2013 Jul 15;8(7):e67051
pubmed: 23869206
PLoS One. 2012;7(3):e32637
pubmed: 22431978
Annu Rev Pharmacol Toxicol. 2000;40:617-47
pubmed: 10836149
Nat Rev Drug Discov. 2021 Sep;20(9):669-688
pubmed: 34006959
Pharmaceuticals (Basel). 2021 May 07;14(5):
pubmed: 34067144
Angew Chem Int Ed Engl. 2018 Dec 21;57(52):17178-17182
pubmed: 30398299
Acta Crystallogr Sect F Struct Biol Cryst Commun. 2010 Sep 1;66(Pt 9):978-84
pubmed: 20823509
J Med Chem. 2017 Mar 9;60(5):1971-1993
pubmed: 28139931
J Am Chem Soc. 2017 Jan 18;139(2):680-685
pubmed: 28051857
Biochim Biophys Acta. 2014 Aug;1843(8):1717-31
pubmed: 24746518
Nat Chem Biol. 2022 Sep;18(9):934-941
pubmed: 35590003
Chem Sci. 2022 Oct 25;13(44):13122-13131
pubmed: 36425501
Structure. 2011 Jun 8;19(6):844-58
pubmed: 21645855
J Med Chem. 2021 Jun 24;64(12):8423-8436
pubmed: 34076416
Theranostics. 2020 Aug 8;10(22):10141-10153
pubmed: 32929339
Chemistry. 2020 Jun 18;26(34):7638-7646
pubmed: 32307728
Structure. 2016 Mar 1;24(3):458-68
pubmed: 26933971
ChemMedChem. 2007 Jan;2(1):58-61
pubmed: 17154430
PLoS Pathog. 2008 Feb 8;4(2):e25
pubmed: 18248095
Acta Crystallogr D Struct Biol. 2018 Feb 1;74(Pt 2):68-84
pubmed: 29533233
ACS Chem Biol. 2017 Feb 17;12(2):504-509
pubmed: 28001046
Bioconjug Chem. 2022 Dec 21;33(12):2370-2380
pubmed: 36383773
J Am Chem Soc. 2021 Dec 8;143(48):20095-20108
pubmed: 34817989
Nat Rev Drug Discov. 2022 Dec;21(12):881-898
pubmed: 36008483
Cell Signal. 2017 Feb;31:26-30
pubmed: 27993556
Bioorg Med Chem. 2018 Jun 1;26(10):2700-2707
pubmed: 28720325
Methods Mol Biol. 2022;2371:63-100
pubmed: 34596844
Semin Cancer Biol. 2006 Jun;16(3):183-92
pubmed: 16697662
Adv Drug Deliv Rev. 2017 Feb;110-111:13-37
pubmed: 27210583
Nat Rev Drug Discov. 2011 Apr;10(4):307-17
pubmed: 21455239
Chem Biol Interact. 2015 Jun 5;234:29-37
pubmed: 25450233
J Med Chem. 2019 Sep 12;62(17):7643-7655
pubmed: 31368705
Chem Sci. 2021 Jul 12;12(32):10836-10847
pubmed: 34476063
Onco Targets Ther. 2013;6:135-43
pubmed: 23493883
Chemistry. 2021 Jan 21;27(5):1487-1513
pubmed: 32875673
Angew Chem Int Ed Engl. 2021 Oct 25;60(44):23750-23755
pubmed: 34472678
Chem. 2022 Oct 13;8(10):2766-2783
pubmed: 35874165
Chembiochem. 2017 Jan 17;18(2):181-184
pubmed: 27966261
Cell Chem Biol. 2017 May 18;24(5):589-597.e5
pubmed: 28434875
J Med Chem. 2019 Oct 24;62(20):9188-9200
pubmed: 31550155
J Am Chem Soc. 2021 Apr 7;143(13):5141-5149
pubmed: 33783207
Chem Commun (Camb). 2019 Jan 25;55(8):1092-1095
pubmed: 30620026
Bioconjug Chem. 2022 Dec 21;33(12):2361-2369
pubmed: 36459098
J Med Chem. 2021 Apr 22;64(8):4903-4912
pubmed: 33797903
ACS Cent Sci. 2022 Jul 27;8(7):955-962
pubmed: 35912347
J Am Chem Soc. 2018 Jan 10;140(1):200-210
pubmed: 29265822
Methods Mol Biol. 2018;1711:133-148
pubmed: 29344888
Nat Chem Biol. 2019 Oct;15(10):937-944
pubmed: 31527835
Curr Opin Chem Biol. 2018 Oct;46:115-122
pubmed: 30059834
Nat Chem Biol. 2020 Feb;16(2):150-159
pubmed: 31768034
Bioconjug Chem. 2022 Oct 19;33(10):1867-1875
pubmed: 36107739
ACS Cent Sci. 2020 Aug 26;6(8):1367-1375
pubmed: 32875077
Chem Biol Interact. 2023 Feb 1;371:110352
pubmed: 36642317
Cell Res. 2005 Apr;15(4):228-36
pubmed: 15857577
Angew Chem Int Ed Engl. 2020 Nov 23;59(48):21520-21524
pubmed: 32816380
Acta Crystallogr D Biol Crystallogr. 2004 Dec;60(Pt 12 Pt 1):2210-21
pubmed: 15572774
Nat Chem Biol. 2021 Mar;17(3):254-262
pubmed: 33398168
J Am Chem Soc. 2022 Oct 12;144(40):18494-18503
pubmed: 36167521
J Am Chem Soc. 2022 Jun 15;144(23):10396-10406
pubmed: 35658467
J Med Chem. 2020 Jan 9;63(1):52-65
pubmed: 31820981
Acta Crystallogr D Struct Biol. 2017 Feb 1;73(Pt 2):112-122
pubmed: 28177307
J Am Chem Soc. 2014 Jun 4;136(22):7877-88
pubmed: 24972345
Nat Protoc. 2016 Dec;11(12):2301-2319
pubmed: 27809316
ChemMedChem. 2016 Sep 20;11(18):1987-94
pubmed: 27331774
J Proteome Res. 2021 Jan 1;20(1):498-505
pubmed: 33332123
J Am Chem Soc. 2021 Sep 1;143(34):13538-13547
pubmed: 34382787
Science. 2005 May 27;308(5726):1318-21
pubmed: 15919995
J Mol Biol. 2011 Jan 14;405(2):607-18
pubmed: 21073878
Adv Drug Deliv Rev. 2017 Sep 15;119:120-142
pubmed: 28506743
J Med Chem. 2020 May 28;63(10):5102-5118
pubmed: 32083858
Cell Chem Biol. 2016 Sep 22;23(9):1123-1134
pubmed: 27617850
Nat Commun. 2020 Aug 26;11(1):4268
pubmed: 32848159
J Am Chem Soc. 2016 Nov 16;138(45):14832-14835
pubmed: 27797495
Nat Rev Drug Discov. 2002 Sep;1(9):727-30
pubmed: 12209152
Acta Crystallogr D Biol Crystallogr. 2013 Jul;69(Pt 7):1204-14
pubmed: 23793146
J Am Chem Soc. 2017 Dec 20;139(50):18365-18375
pubmed: 29206031
Mol Cell Proteomics. 2021;20:100077
pubmed: 33813065
ChemMedChem. 2020 Nov 18;15(22):2176-2184
pubmed: 32790900
Cell Chem Biol. 2019 Jan 17;26(1):98-108.e5
pubmed: 30449673
Chem Biol. 2013 Aug 22;20(8):973-82
pubmed: 23891150
J Med Chem. 2019 Jun 13;62(11):5616-5627
pubmed: 31095386
J Med Chem. 2018 Jul 26;61(14):6350-6363
pubmed: 29940121
Proc Natl Acad Sci U S A. 1999 Dec 21;96(26):14694-9
pubmed: 10611275
J Am Chem Soc. 2022 Jan 19;144(2):701-708
pubmed: 34994556
Bioorg Med Chem Lett. 2012 May 15;22(10):3492-7
pubmed: 22507964
Nucleic Acids Res. 2022 Jan 7;50(D1):D543-D552
pubmed: 34723319
J Appl Crystallogr. 2007 Aug 1;40(Pt 4):658-674
pubmed: 19461840
Nat Methods. 2020 Jul;17(7):665-680
pubmed: 32483333
Bioconjug Chem. 2014 May 21;25(5):989-99
pubmed: 24738859
Aliment Pharmacol Ther. 2006 Jun;23 Suppl 2:2-8
pubmed: 16700898
Chem Commun (Camb). 2023 Feb 7;59(12):1697-1700
pubmed: 36692261
J Am Chem Soc. 2020 Jul 8;142(27):11734-11742
pubmed: 32369353
Curr Opin Chem Biol. 2019 Feb;48:96-105
pubmed: 30508703
Chem Commun (Camb). 2016 Apr 14;52(29):5140-3
pubmed: 26996321
Mol Cell Biochem. 2012 Jan;360(1-2):261-70
pubmed: 21948273
RSC Chem Biol. 2021 Aug 16;2(5):1474-1478
pubmed: 34704051
Nat Chem Biol. 2014 Sep;10(9):760-767
pubmed: 25038787
J Am Chem Soc. 2022 Aug 24;144(33):15303-15313
pubmed: 35945166
Nat Commun. 2020 Oct 7;11(1):5047
pubmed: 33028810
J Comput Aided Mol Des. 2022 Nov;36(11):825-835
pubmed: 36258137
Elife. 2022 Dec 28;11:
pubmed: 36576241
Nat Chem Biol. 2019 Jul;15(7):737-746
pubmed: 31209349