Protein-Observed Fluorine NMR: A Bioorthogonal Approach for Small Molecule Discovery.
J Med Chem. 2015 Nov 24;
Authors: Arntson KE, Pomerantz WC
Abstract
The 19F isotope is 100% naturally abundant and is the second most sensitive and stable NMR-active nucleus. Unlike the ubiquitous hydrogen atom, fluorine is nearly absent in biological systems, making it a unique bioorthogonal atom for probing molecular interactions in biology. Over 73 fluorinated proteins have been studied by 19F NMR since the seminal studies of Hull and Sykes in 1974. With advances in cryoprobe production and fluorinated amino acid incorporation strategies, protein-based 19F NMR offers opportunities to the medicinal chemist for characterizing and ultimately discovering new small molecule protein ligands. This perspective will highlight new advances using 19F NMR for characterizing small molecule interactions with both small and large proteins as well as detailing NMR resonance assignment challenges and amino acid incorporation approaches.
PMID: 26599421 [PubMed - as supplied by publisher]
[NMR paper] Dual screening of BPTF and Brd4 using protein-observed fluorine NMR uncovers new bromodomain probe molecules.
Dual screening of BPTF and Brd4 using protein-observed fluorine NMR uncovers new bromodomain probe molecules.
Dual screening of BPTF and Brd4 using protein-observed fluorine NMR uncovers new bromodomain probe molecules.
ACS Chem Biol. 2015 Jul 9;
Authors: Urick AK, Hawk LM, Cassel MK, Mishra NK, Liu S, Adhikari N, Zhang W, Dos Santos CO, Hall JL, Pomerantz WC
Abstract
Bromodomain-containing protein dysregulation is linked to cancer, diabetes, and inflammation. Selec-tive inhibition of bromodomain function is a newly...
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[NMR paper] TROSY NMR with a 52 kDa sugar transport protein and the binding of a small-molecule inhibitor.
TROSY NMR with a 52 kDa sugar transport protein and the binding of a small-molecule inhibitor.
Related Articles TROSY NMR with a 52 kDa sugar transport protein and the binding of a small-molecule inhibitor.
Mol Membr Biol. 2014 May 7;
Authors: Kalverda AP, Gowdy J, Thompson GS, Homans SW, Henderson PJ, Patching SG
Abstract
Abstract Using the sugar transport protein, GalP, from Escherichia coli, which is a homologue of human GLUT transporters, we have overcome the challenges for achieving high-resolution - and -methyl-TROSY NMR...
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05-09-2014 07:01 PM
Antidiabetic effects of glucokinase regulatory protein small-molecule disruptors - Nature.com
Antidiabetic effects of glucokinase regulatory protein small-molecule disruptors - Nature.com
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Antidiabetic effects of glucokinase regulatory protein small-molecule disruptors
Nature.com
In hepatocytes, GK regulates glucose uptake and glycogen synthesis, suppresses glucose production3, 5, and is subject to the endogenous inhibitor GK regulatory protein (GKRP)6, 7, 8. During fasting, GKRP binds, inactivates and ..... 1H-, 13C- and 19F ...
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11-16-2013 03:09 AM
[NMR paper] Screening protein-small molecule interactions by NMR.
Screening protein-small molecule interactions by NMR.
Related Articles Screening protein-small molecule interactions by NMR.
Methods Mol Biol. 2013;1008:389-413
Authors: Davis B
Abstract
Nuclear magnetic resonance (NMR) is well suited to probing the interactions between ligands and macromolecular receptors. It is a truly label-free technique, requiring only the presence of atoms (usually (1)H or (19)F) which give rise to observable resonances on either the ligand or the receptor. A number of parameters associated with these resonances can...
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[CNS Yahoo group] How to add bond between protein residue and a small molecule in CNS
How to add bond between protein residue and a small molecule in CNS
Dear All, I'm stuck in a step where in i need to connect a bond an amino acid residue and a small molecule in CNS Thank you. Joseph
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08-07-2011 01:35 AM
Two-dimensional concurrent HMQC-COSY as an approach for small molecule chemical shift assignment and compound identification
Two-dimensional concurrent HMQC-COSY as an approach for small molecule chemical shift assignment and compound identification
Abstract Chemical shift assignment is the first step toward the structure elucidation of natural products and other chemical compounds. We propose here the use of 2D concurrent HMQC-COSY as an experiment for rapid chemical shift assignment of small molecules. This experiment provides well-dispersed 1Hâ??13C peak patterns that are distinctive for different functional groups plus 1Hâ??1H COSY connectivities that serve to identify adjacent groups. The COSY diagonal...
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Preparation of protein samples for NMR structure, function, and small-molecule screening studies.
Preparation of protein samples for NMR structure, function, and small-molecule screening studies.
Preparation of protein samples for NMR structure, function, and small-molecule screening studies.
Methods Enzymol. 2011;493:21-60
Authors: Acton TB, Xiao R, Anderson S, Aramini J, Buchwald WA, Ciccosanti C, Conover K, Everett J, Hamilton K, Huang YJ, Janjua H, Kornhaber G, Lau J, Lee DY, Liu G, Maglaqui M, Ma L, Mao L, Patel D, Rossi P, Sahdev S, Shastry R, Swapna GV, Tang Y, Tong S, Wang D, Wang H, Zhao L, Montelione GT
In this chapter, we...
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Small Molecule NMR Scientist (B.S./ M.S.) at Novartis Ag (Cambridge, MA)
Small Molecule NMR Scientist (B.S./ M.S.) at Novartis Ag (Cambridge, MA)
using the state-of-the-art NMR methodologies. As an NMR scientist within the team, you will be responsible for ... in small molecular NMR with demonstrated success in modern NMR methodologies. Demonstrated skills in data collection...
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Protein-Observed Fluorine NMR: A Bioorthogonal Approach for Small Molecule Discovery.
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