Recently, there has been increasing interest in new modalities such as therapeutic antibodies and gene therapy at a number of pharmaceutical companies. Moreover, in small-molecule drug discovery at such companies, efforts have focused on hard-to-drug targets such as inhibiting proteinâ??protein interactions. Biomolecular NMR spectroscopy has been used in drug discovery in a variety of ways, such as for the reliable detection of binding and providing three-dimensional structural information for structure-based drug design. The advantages of using NMR spectroscopy have been known for decades (Jahnke in J Biomol NMR 39:87â??90, (2007); Gossert and Jahnke in Prog Nucl Magn Reson Spectrosc 97:82â??125, (2016)). For tackling hard-to-drug targets and increasing the success in discovering drug molecules, in-depth analysis of drugâ??target protein interactions performed by biophysical methods will be more and more essential. Here, we review the advantages of NMR spectroscopy as a key technology of biophysical methods and also discuss issues such as using cutting-edge NMR spectrometers and increasing the demand of utilizing conformational dynamics information for promoting small-molecule drug discovery.
[NMR paper] Discovery of Small-Molecule Inhibitors of Ubiquitin Specific Protease 7 (USP7) Using Integrated NMR and in Silico Techniques.
Discovery of Small-Molecule Inhibitors of Ubiquitin Specific Protease 7 (USP7) Using Integrated NMR and in Silico Techniques.
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J Med Chem. 2017 12 28;60(24):10056-10070
Authors: Di Lello P, Pastor R, Murray JM, Blake RA, Cohen F, Crawford TD, Drobnick J, Drummond J, Kategaya L, Kleinheinz T, Maurer T,...
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[NMR paper] Solution NMR Spectroscopy in Target-Based Drug Discovery.
Solution NMR Spectroscopy in Target-Based Drug Discovery.
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Molecules. 2017 Aug 23;22(9):
Authors: Li Y, Kang C
Abstract
Solution NMR spectroscopy is a powerful tool to study protein structures and dynamics under physiological conditions. This technique is particularly useful in target-based drug discovery projects as it provides protein-ligand binding information in solution. Accumulated studies have shown that NMR will play more and more important...
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[NMR paper] Protein-Observed Fluorine NMR: A Bioorthogonal Approach for Small Molecule Discovery.
Protein-Observed Fluorine NMR: A Bioorthogonal Approach for Small Molecule Discovery.
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...
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[NMR paper] Fragment-based drug discovery using NMR spectroscopy.
Fragment-based drug discovery using NMR spectroscopy.
Related Articles Fragment-based drug discovery using NMR spectroscopy.
J Biomol NMR. 2013 May 18;
Authors: Harner MJ, Frank AO, Fesik SW
Abstract
Nuclear magnetic resonance (NMR) spectroscopy has evolved into a powerful tool for fragment-based drug discovery over the last two decades. While NMR has been traditionally used to elucidate the three-dimensional structures and dynamics of biomacromolecules and their interactions, it can also be a very valuable tool for the reliable...
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Small-Molecule Binding Sites on Proteins Establishedby Paramagnetic NMR Spectroscopy
Small-Molecule Binding Sites on Proteins Establishedby Paramagnetic NMR Spectroscopy
Jia-Ying Guan, Peter H. J. Keizers, Wei-Min Liu, Frank Lo?hr, Simon P. Skinner, Edwin A. Heeneman, Harald Schwalbe, Marcellus Ubbink and Gregg Siegal
http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/jacsat/0/jacsat.ahead-of-print/ja401323m/aop/images/medium/ja-2013-01323m_0009.gif
Journal of the American Chemical Society
DOI: 10.1021/ja401323m
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[NMR paper] Small molecule binding sites on proteins established by paramagnetic NMR spectroscopy.
Small molecule binding sites on proteins established by paramagnetic NMR spectroscopy.
Related Articles Small molecule binding sites on proteins established by paramagnetic NMR spectroscopy.
J Am Chem Soc. 2013 Mar 20;
Authors: Guan JY, Keizers PH, Liu WM, Loehr F, Skinner SP, Heeneman EA, Schwalbe H, Ubbink M, Siegal GD
Abstract
Determining the three dimensional structure of a small molecule-protein complex with weak affinity can be a significant challenge. We present a paramagnetic NMR method to determine intermolecular structure...
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[NMR paper] Flow NMR spectroscopy in drug discovery.
Flow NMR spectroscopy in drug discovery.
Related Articles Flow NMR spectroscopy in drug discovery.
Curr Opin Drug Discov Devel. 2000 May;3(3):269-74
Authors: Stockman BJ
Flow NMR spectroscopy techniques are becoming increasingly utilized in drug discovery and development. LC-NMR has become a routine method to resolve and identify mixture components. It has broad applications in natural products biochemistry, and drug metabolism and toxicology studies. The rapid throughput of direct-injection NMR of biofluids, combinatorial chemistry samples...
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Application of NMR Spectroscopy in Medicinal Chemistry and Drug Discovery.
Application of NMR Spectroscopy in Medicinal Chemistry and Drug Discovery.
Related Articles Application of NMR Spectroscopy in Medicinal Chemistry and Drug Discovery.
Curr Top Med Chem. 2010 Sep 2;
Authors: Ohno A, Inomata K, Tochio H, Shirakawa M
"In-cell nuclear magnetic resonance (NMR)" is a unique method for characterization of conformation, interaction and dynamics of proteins inside living cells at atomic level. Since the method was proposed by Dötch and co-workers in 2001 , its application had been limited to bacterial cells and...
Revisiting biomolecular NMR spectroscopy for promoting small-molecule drug discovery
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