Proteomics

Dataset Information

0

Sulfamate acetamides as self-immolative electrophiles for covalent ligand- directed release chemistry


ABSTRACT: Electrophiles for covalent inhibitors that are suitable for in vivo administration are rare. While acrylamides are prevalent in FDA approved covalent drugs, chloroacetamides are considered too reactive for such purposes. We report sulfamate-based electrophiles that maintain chloroacetamide-like geometry, with tunable reactivity. We prepared sulfamate-based inhibitors for BTK and Pin1 displaying high potency, low intrinsic reactivity and high stability. Finally, we show that sulfamate acetamides can be used for covalent ligand-directed release (CoLDR) chemistry, both for the generation of ‘turn-on’ probes as well as for traceless ligand-directed site-specific labeling of proteins. Using alkyne-modified sulfamate-based probes, we performed proteomics studies with samples enriched with probe-bound proteins, and the sulfamate probes displayed comparable or improved selectivity compared to the parent compounds. Further characterization of off-target using IsoDTB-ABPP confirmed this result. This submission contains the IsoDTB data.

INSTRUMENT(S): Orbitrap Exploris 240

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Pancreatic Duct

DISEASE(S): Adenocarcinoma,Carcinoma

SUBMITTER: Ronen Gabizon  

LAB HEAD: Nir London

PROVIDER: PXD038301 | Pride | 2023-03-11

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
Ram_Mino_1267_1.raw Raw
Ram_Mino_1267_2.raw Raw
Ram_Mino_1267_3.raw Raw
Ram_Mino_1267_4.raw Raw
Ram_Mino_Ibrutinib_1.raw Raw
Items per page:
1 - 5 of 23
altmetric image

Publications


Electrophiles for covalent inhibitors that are suitable for in vivo administration are rare. While acrylamides are prevalent in FDA-approved covalent drugs, chloroacetamides are considered too reactive for such purposes. We report sulfamate-based electrophiles that maintain chloroacetamide-like geometry with tunable reactivity. In the context of the BTK inhibitor ibrutinib, sulfamate analogues showed low reactivity with comparable potency in protein labeling, in vitro, and cellular kinase activi  ...[more]

Similar Datasets

2023-03-11 | PXD038375 | Pride
2019-12-02 | PXD015457 | Pride
2022-04-19 | PXD031708 | Pride
2020-04-14 | PXD016659 | Pride
2024-01-26 | PXD033546 | Pride
2021-09-20 | PXD025829 | Pride
2024-04-23 | PXD047840 | Pride
2021-08-04 | GSE135190 | GEO
2021-11-02 | PXD023707 | Pride
2022-02-28 | PXD009657 | Pride