Methyl lysine readers, specifically PHD fingers, are emerging epigenetic targets in human diseases. For example, several PHD finger fusions are implicated in clinical cases of acute myeloid leukemia, highlighting the potential for PHD inhibitors in disease regulation. However, limited chemical matter targeting PHD fingers exists. Here we report the first fragment-based screen against the BPTF PHD to identify several of the first reported BPTF PHD-targeting small-molecule ligands. We used...
[NMR paper] NMR fragment screening reveals a novel small molecule binding site near the catalytic surface of the disulfide-dithiol oxidoreductase enzyme DsbA from Burkholderia pseudomallei.
NMR fragment screening reveals a novel small molecule binding site near the catalytic surface of the disulfide-dithiol oxidoreductase enzyme DsbA from Burkholderia pseudomallei.
Related Articles NMR fragment screening reveals a novel small molecule binding site near the catalytic surface of the disulfide-dithiol oxidoreductase enzyme DsbA from Burkholderia pseudomallei.
J Biomol NMR. 2020 Aug 06;:
Authors: Nebl S, Alwan WS, Williams ML, Sharma G, Taylor A, Doak BC, Wilde KL, McMahon RM, Halili MA, Martin JL, Capuano B, Fenwick RB, Mohanty B, Scanlon...
nmrlearner
Journal club
0
08-08-2020 10:56 PM
NMR fragment screening reveals a novel small molecule binding site near the catalytic surface of the disulfideâ??dithiol oxidoreductase enzyme DsbA from Burkholderia pseudomallei
NMR fragment screening reveals a novel small molecule binding site near the catalytic surface of the disulfideâ??dithiol oxidoreductase enzyme DsbA from Burkholderia pseudomallei
Abstract
The presence of suitable cavities or pockets on protein structures is a general criterion for a therapeutic target protein to be classified as â??druggableâ??. Many disease-related proteins that function solely through proteinâ??protein interactions lack such pockets, making development of inhibitors by traditional small-molecule structure-based design methods much...
nmrlearner
Journal club
0
08-06-2020 12:03 PM
[NMR paper] Thiourea-Based Inhibitors of the B-Cell Lymphoma 6 (BCL6) BTB Domain via NMR-Based Fragment Screening and Computer-Aided Drug Design.
Thiourea-Based Inhibitors of the B-Cell Lymphoma 6 (BCL6) BTB Domain via NMR-Based Fragment Screening and Computer-Aided Drug Design.
Related Articles Thiourea-Based Inhibitors of the B-Cell Lymphoma 6 (BCL6) BTB Domain via NMR-Based Fragment Screening and Computer-Aided Drug Design.
J Med Chem. 2018 Jul 03;:
Authors: Cheng H, Linhares B, Yu W, Cardenas MG, Ai Y, Jiang W, Winkler A, Cohen S, Melnick A, MacKerell AD, Cierpicki T, Xue F
Abstract
Protein-protein interactions (PPI) between the transcriptional repressor B-cell...
nmrlearner
Journal club
0
07-06-2018 09:40 AM
[NMR paper] Dual Labeling of the CBP/p300 KIX domain for 19F NMR leads to identification of a new small molecule binding site.
Dual Labeling of the CBP/p300 KIX domain for 19F NMR leads to identification of a new small molecule binding site.
Dual Labeling of the CBP/p300 KIX domain for 19F NMR leads to identification of a new small molecule binding site.
Chembiochem. 2018 Feb 11;:
Authors: Gee CT, Arntson KE, Koleski EJ, Staebell RL, Pomerantz WCK
Abstract
Protein-Observed Fluorine NMR Spectroscopy (PrOF NMR) is an emerging technique for screening and characterizing small molecule-protein interactions. The choice of which amino acid to label for PrOF...
nmrlearner
Journal club
0
02-14-2018 02:43 AM
[NMR paper] Evaluation of ligand-based NMR screening methods to characterize small molecule binding to HIV-1 glycoprotein-41.
Evaluation of ligand-based NMR screening methods to characterize small molecule binding to HIV-1 glycoprotein-41.
Related Articles Evaluation of ligand-based NMR screening methods to characterize small molecule binding to HIV-1 glycoprotein-41.
Org Biomol Chem. 2017 Jun 07;:
Authors: Chu S, Zhou G, Gochin M
Abstract
Small molecule inhibitors of glycoprotein-41 (gp41) are able to prevent HIV infection by binding to a hydrophobic pocket (HP) contained within the gp41 ectodomain, and preventing progression of fusion. There is little...
nmrlearner
Journal club
0
06-08-2017 07:00 PM
[NMR paper] Identification of Small-Molecule Inhibitors of the HuR/RNA Interaction Using a Fluorescence Polarization Screening Assay Followed by NMR Validation.
Identification of Small-Molecule Inhibitors of the HuR/RNA Interaction Using a Fluorescence Polarization Screening Assay Followed by NMR Validation.
Related Articles Identification of Small-Molecule Inhibitors of the HuR/RNA Interaction Using a Fluorescence Polarization Screening Assay Followed by NMR Validation.
PLoS One. 2015;10(9):e0138780
Authors: Wang Z, Bhattacharya A, Ivanov DN
Abstract
The human antigen R (HuR) stabilizes many mRNAs of proto-oncogene, transcription factors, cytokines and growth factors by recognizing...
nmrlearner
Journal club
0
09-22-2015 06:40 PM
Fragment-based discovery of novel thymidylate synthase leads by NMR screening and group epitope mapping.
Fragment-based discovery of novel thymidylate synthase leads by NMR screening and group epitope mapping.
Fragment-based discovery of novel thymidylate synthase leads by NMR screening and group epitope mapping.
Chem Biol Drug Des. 2010 Sep 1;76(3):218-33
Authors: Begley DW, Zheng S, Varani G
Solution-state nuclear magnetic resonance (NMR) is a versatile tool for the study of binding interactions between small molecules and macromolecular targets. We applied ligand-based NMR techniques to the study of human thymidylate synthase (hTS) using known...
nmrlearner
Journal club
0
01-05-2011 09:51 PM
Novel Small Molecule Inhibitors of MDR Mycobacterium tuberculosis by NMR Fragment Scr
Novel Small Molecule Inhibitors of MDR Mycobacterium tuberculosis by NMR Fragment Screening of Antigen 85C.
Related Articles Novel Small Molecule Inhibitors of MDR Mycobacterium tuberculosis by NMR Fragment Screening of Antigen 85C.
J Med Chem. 2010 Nov 12;
Authors: Scheich C, Puetter V, Schade M
Protein target-based discovery of novel antibiotics has been largely unsuccessful despite rich genome information. Particularly in need are new antibiotics for tuberculosis, which kills 1.6 million people annually and shows a rapid increase in...
Fragment-Based NMR Screening of the BPTF PHD Finger Methyl Lysine Reader Leads to the First Small-Molecule Inhibitors
Linear Mode
