Perspectives on Applications of 19F-NMR in Fragment-Based Drug Discovery DOI Creative Commons
Qingxin Li, CongBao Kang

Molecules, Journal Year: 2024, Volume and Issue: 29(23), P. 5748 - 5748

Published: Dec. 5, 2024

Fragment-based drug discovery is a powerful approach in discovery, applicable to wide range of targets. This method enables the potent compounds that can modulate target functions, starting from fragment bind weakly While biochemical, biophysical, and cell-based assays are commonly used identify fragments,

Language: Английский

Fragment Screening Identifies Novel Allosteric Binders and Binding Sites in the VHR (DUSP3) Phosphatase DOI Creative Commons
Jiaqian Wu, Marek R. Baranowski, Alexander E. Aleshin

et al.

ACS Omega, Journal Year: 2025, Volume and Issue: 10(5), P. 4912 - 4926

Published: Jan. 31, 2025

The human Vaccinia H1-related phosphatase (VHR; DUSP3) is a critical positive regulator of the innate immune response. Recent studies suggest that inhibiting VHR could be beneficial in treating sepsis and septic shock. belongs to superfamily protein tyrosine phosphatases (PTPs), large class enzymes are notoriously difficult target with small molecules. Fragment-based drug discovery (FBDD) has emerged as an effective strategy for generating potent ligands, even challenging targets. Here, we present fluorine NMR-based platform identifying fragments bind VHR. This encompasses automated library assembly, mixture formation, quantitative material transfer, NMR screening, biophysical hit confirmation. We demonstrate this streamlined, integrated screening workflow produces validated hits diverse chemical matter tangible structure-activity relationships (SAR). Crystal structures yielded detailed information on fragment-protein interactions provide basis future structurally enabled ligand optimization. Notably, discovered novel binding sites VHR, distant from conserved active site, facilitating generation selective modulators. fragment can applied other PTPs holds significant potential ligands.

Language: Английский

Citations

0
Synthesis and evaluation of fluorinated tetrahydrocarbazoles as probes in NMR based binding assay of the E. coli β sliding clamp DOI Creative Commons
Cecilie Elisabeth Olsen, Signe Simonsen,

Srinivas Reddy Merugu

et al.

Bioorganic & Medicinal Chemistry, Journal Year: 2025, Volume and Issue: 122, P. 118139 - 118139

Published: Feb. 27, 2025

Language: Английский

Citations

0
NMR investigations of glycan conformation, dynamics, and interactions DOI
Jesús Angulo, Ana Ardá, Sara Bertuzzi

et al.

Progress in Nuclear Magnetic Resonance Spectroscopy, Journal Year: 2024, Volume and Issue: 144-145, P. 97 - 152

Published: Oct. 12, 2024

Language: Английский

Citations

3
Perspectives on Applications of 19F-NMR in Fragment-Based Drug Discovery DOI Creative Commons
Qingxin Li, CongBao Kang

Molecules, Journal Year: 2024, Volume and Issue: 29(23), P. 5748 - 5748

Published: Dec. 5, 2024

Fragment-based drug discovery is a powerful approach in discovery, applicable to wide range of targets. This method enables the potent compounds that can modulate target functions, starting from fragment bind weakly While biochemical, biophysical, and cell-based assays are commonly used identify fragments,

Language: Английский

Citations

1