Facile Synthesis of Homodimeric Protein Ligands.
bivalent
degrader
homodimer
ligand
pyridone
Journal
Chembiochem : a European journal of chemical biology
ISSN: 1439-7633
Titre abrégé: Chembiochem
Pays: Germany
ID NLM: 100937360
Informations de publication
Date de publication:
15 09 2023
15 09 2023
Historique:
revised:
11
07
2023
received:
07
06
2023
pmc-release:
15
09
2024
medline:
18
9
2023
pubmed:
14
7
2023
entrez:
14
7
2023
Statut:
ppublish
Résumé
Many proteins exist as oligomers (homodimers, homotrimers, etc.). A proven strategy for the development of high affinity ligands for such targets is to link together two modest affinity ligands that allows the formation of a 2 : 2 (or higher-order) protein-ligand complex. We report here the discovery of a convenient, "click-like" reaction for the homodimerization of protein ligands that is efficient, operationally simple to carry out, and tolerant of many functional groups. This chemistry reduces the synthetic burden inherent in the creation of homodimeric ligands since only a single precursor is required. The utility of this strategy is demonstrated by the synthesis of homodimeric inhibitors, including PROTACs.
Identifiants
pubmed: 37449865
doi: 10.1002/cbic.202300392
pmc: PMC10615197
mid: NIHMS1934610
doi:
Substances chimiques
Ligands
0
Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
e202300392Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM133041
Pays : United States
Informations de copyright
© 2023 The Authors. ChemBioChem published by Wiley-VCH GmbH.
Références
Drug Discov Today. 2021 Jan;26(1):189-199
pubmed: 33075471
Beilstein J Org Chem. 2013 Nov 28;9:2681-7
pubmed: 24367433
Cell Chem Biol. 2021 Jul 15;28(7):934-951
pubmed: 34004187
Br J Cancer. 2021 Apr;124(9):1478-1490
pubmed: 33723398
Curr Opin Chem Biol. 2000 Dec;4(6):696-703
pubmed: 11102876
J Am Chem Soc. 2008 Apr 30;130(17):5744-52
pubmed: 18386897
Nature. 2010 Dec 23;468(7327):1067-73
pubmed: 20871596
Nat Chem Biol. 2017 May;13(5):514-521
pubmed: 28288108
Bioorg Med Chem Lett. 2020 May 15;30(10):127104
pubmed: 32201020
Chem Soc Rev. 2022 Aug 15;51(16):7066-7114
pubmed: 35916511
Mol Cells. 2018 Nov 30;41(11):933-942
pubmed: 30486612
Angew Chem Int Ed Engl. 2012 Oct 15;51(42):10472-98
pubmed: 22952048
Cell. 2011 Sep 16;146(6):904-17
pubmed: 21889194
J Med Chem. 2018 Jan 25;61(2):462-481
pubmed: 28339196
Nat Chem Biol. 2016 Dec;12(12):1089-1096
pubmed: 27775715
Curr Opin Chem Biol. 2018 Jun;44:47-55
pubmed: 29885948
ACS Med Chem Lett. 2017 Mar 01;8(4):407-412
pubmed: 28435527
Nat Rev Drug Discov. 2022 Mar;21(3):181-200
pubmed: 35042991
Nat Rev Drug Discov. 2021 Apr;20(4):247-250
pubmed: 33737725
Proc Natl Acad Sci U S A. 1998 Jul 21;95(15):8817-22
pubmed: 9671762
Nat Commun. 2017 Oct 10;8(1):830
pubmed: 29018234
Front Pharmacol. 2019 Nov 08;10:1315
pubmed: 31780938
Proc Natl Acad Sci U S A. 2000 Jul 18;97(15):8507-12
pubmed: 10900011
Nat Rev Drug Discov. 2019 Dec;18(12):949-963
pubmed: 31666732
Drug Discov Today Technol. 2019 Apr;31:15-27
pubmed: 31200855
BMC Cancer. 2009 Jul 14;9:229
pubmed: 19602254
J Oleo Sci. 2014;63(9):939-42
pubmed: 25099910
Angew Chem Int Ed Engl. 2016 Jan 11;55(2):807-10
pubmed: 26593377
FEBS Lett. 2002 Feb 20;513(1):124-8
pubmed: 11911891
Science. 2015 Feb 13;347(6223):779-84
pubmed: 25678665
Nature. 2011 Aug 03;478(7370):524-8
pubmed: 21814200
Angew Chem Int Ed Engl. 2003 Apr 29;42(17):1900-23
pubmed: 12730969
Nat Chem Biol. 2010 Mar;6(3):162-165
pubmed: 20154660
ACS Chem Biol. 2015 Aug 21;10(8):1770-7
pubmed: 26035625
J Med Chem. 2012 Dec 13;55(23):10584-600
pubmed: 23181587
J Biol Chem. 2018 Oct 26;293(43):16761-16777
pubmed: 30206124
Angew Chem Int Ed Engl. 2009;48(51):9685-9
pubmed: 19937879
Chem Rev. 2021 Jul 14;121(13):7638-7956
pubmed: 34165284
Chembiochem. 2022 Sep 16;23(18):e202200275
pubmed: 35802347
ChemMedChem. 2019 Apr 17;14(8):842-852
pubmed: 30829448
Angew Chem Int Ed Engl. 2021 Feb 15;60(7):3346-3354
pubmed: 32410219
Cell Chem Biol. 2020 Aug 20;27(8):998-1014
pubmed: 32795419
Cell. 2020 Apr 2;181(1):102-114
pubmed: 31955850
Angew Chem Int Ed Engl. 2006 Apr 3;45(15):2348-68
pubmed: 16557636
Nat Chem Biol. 2021 Nov;17(11):1157-1167
pubmed: 34675414
ACS Chem Biol. 2016 Mar 18;11(3):598-608
pubmed: 26596782
Bioorg Med Chem. 2019 Feb 1;27(3):447-456
pubmed: 30606670
Nat Rev Cancer. 2017 Aug;17(8):502-508
pubmed: 28643779
J Oleo Sci. 2008;57(1):53-4
pubmed: 18075223
J Med Chem. 2019 May 23;62(10):4851-4883
pubmed: 30516990