Fragment Screening Yields a Small‐Molecule Stabilizer of 14‐3‐3 Dimers That Modulates Client Protein Interactions
Sign Up to like & getrecommendations! Published in 2022 at "Chembiochem"
DOI: 10.1002/cbic.202200178
Abstract: The development of protein‐protein interaction (PPI) inhibitors has been a successful strategy in drug development. However, the identification of PPI stabilizers has proven much more challenging. Here we report a fragment‐based drug screening approach using… read more here.
Keywords: client protein; fragment screening; stabilizer; protein interactions ... See more keywords
Large-Scale Crystallographic Fragment Screening Expedites Compound Optimization and Identifies Putative Protein-Protein Interaction Sites.
Sign Up to like & getrecommendations! Published in 2022 at "Journal of medicinal chemistry"
DOI: 10.1021/acs.jmedchem.2c01165
Abstract: The identification of starting points for compound development is one of the key steps in early-stage drug discovery. Information-rich techniques such as crystallographic fragment screening can potentially increase the efficiency of this step by providing… read more here.
Keywords: protein protein; interaction sites; fragment screening; crystallographic fragment ... See more keywords
Halo Library, a Tool for Rapid Identification of Ligand Binding Sites on Proteins Using Crystallographic Fragment Screening
Sign Up to like & getrecommendations! Published in 2022 at "Journal of Medicinal Chemistry"
DOI: 10.1021/acs.jmedchem.2c01681
Abstract: X-ray crystallographic fragment screening (XCFS) uses fragment-sized molecules (∼60 – 300 Da) to access binding sites on proteins that may be inaccessible to larger drug-like molecules (>300 Da). Previous studies from our lab and others… read more here.
Keywords: sites proteins; fragment; fragment screening; halo library ... See more keywords
Affinity Mass Spectrometry-Based Fragment Screening Identified a New Negative Allosteric Modulator of the Adenosine A2A Receptor Targeting the Sodium Ion Pocket.
Sign Up to like & getrecommendations! Published in 2021 at "ACS chemical biology"
DOI: 10.1021/acschembio.0c00899
Abstract: Allosteric ligands provide new opportunities to modulate G protein-coupled receptor (GPCR) function and present therapeutic benefits over orthosteric molecules. Negative allosteric modulators (NAMs) can inhibit the activation of a receptor and downstream signal transduction. Screening… read more here.
Keywords: fragment screening; mass spectrometry; affinity mass; negative allosteric ... See more keywords
Crystal structures and fragment screening of SARS-CoV-2 NSP14 reveal details of exoribonuclease activation and mRNA capping and provide starting points for antiviral drug development
Sign Up to like & getrecommendations! Published in 2022 at "Nucleic Acids Research"
DOI: 10.1093/nar/gkac1207
Abstract: The SARS-CoV-2 non-structural protein 14 (NSP14) is a dual function enzyme containing an N-terminal exonuclease domain (ExoN) and C-terminal Guanine-N7-methyltransferase (N7-MTase) domain. Both enzymatic activities appear to be essential for the viral life cycle and… read more here.
Keywords: reveal; structure; mrna capping; fragment screening ... See more keywords
Fragment Screening of Human Kynurenine Aminotransferase-II
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DOI: 10.1177/2472555218764620
Abstract: Kynurenine aminotransferase-II (KAT-II) is a pyridoxal 5′-phosphate (PLP)–dependent enzyme that acts in the tryptophan metabolic pathway by catalyzing the transamination of kynurenine into kynurenic acid (KYNA). It is one of four isoforms in the KAT… read more here.
Keywords: kynurenine; kynurenine aminotransferase; fragment screening; screening human ... See more keywords
Mapping major SARS-CoV-2 drug targets and assessment of druggability using computational fragment screening: Identification of an allosteric small-molecule binding site on the Nsp13 helicase.
Sign Up to like & getrecommendations! Published in 2021 at "PloS one"
DOI: 10.1371/journal.pone.0246181
Abstract: The 2019 emergence of, SARS-CoV-2 has tragically taken an immense toll on human life and far reaching impacts on society. There is a need to identify effective antivirals with diverse mechanisms of action in order… read more here.
Keywords: drug; small molecule; site; fragment screening ... See more keywords
Novel Starting Points for Human Glycolate Oxidase Inhibitors, Revealed by Crystallography-Based Fragment Screening
Sign Up to like & getrecommendations! Published in 2022 at "Frontiers in Chemistry"
DOI: 10.3389/fchem.2022.844598
Abstract: Primary hyperoxaluria type I (PH1) is caused by AGXT gene mutations that decrease the functional activity of alanine:glyoxylate aminotransferase. A build-up of the enzyme’s substrate, glyoxylate, results in excessive deposition of calcium oxalate crystals in… read more here.
Keywords: glycolate oxidase; crystallography; fragment screening; oxidase ... See more keywords