Inverse Drug Discovery identifies weak electrophiles affording protein conjugates.
Inverse drug discovery
Latent electrophile
Sulfur(VI)-fluoride exchange (SuFEx)
Journal
Current opinion in chemical biology
ISSN: 1879-0402
Titre abrégé: Curr Opin Chem Biol
Pays: England
ID NLM: 9811312
Informations de publication
Date de publication:
04 2022
04 2022
Historique:
received:
14
10
2021
revised:
13
12
2021
accepted:
20
12
2021
pubmed:
23
1
2022
medline:
29
3
2022
entrez:
22
1
2022
Statut:
ppublish
Résumé
Traditional biochemical target-based and phenotypic cell-based screening approaches to drug discovery have produced the current covalent and non-covalent pharmacopoeia. Strategies to expand the druggable proteome include Inverse Drug Discovery, which involves incubating one weak organic electrophile at a time with the proteins of a living cell to identify the conjugates formed. An alkyne substructure in each organic electrophile enables affinity chromatography-mass spectrometry, which produces a list of proteins that each distinct compound reacts with. Herein, we review Inverse Drug Discovery in the context of organic compounds of intermediate complexity harboring Sulfur(VI)-fluoride exchange (SuFEx) electrophiles used to expand the cellular proteins that can be targeted covalently.
Identifiants
pubmed: 35065430
pii: S1367-5931(21)00158-7
doi: 10.1016/j.cbpa.2021.102113
pmc: PMC8940698
mid: NIHMS1773532
pii:
doi:
Substances chimiques
Proteins
0
Sulfur
70FD1KFU70
Fluorides
Q80VPU408O
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
102113Subventions
Organisme : NIGMS NIH HHS
ID : P41 GM103311
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK046335
Pays : United States
Informations de copyright
Copyright © 2022 Elsevier Ltd. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors declare that they have no competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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