scholarly journals Anchoring protein crystals to mounting loops with hydrogel using inkjet technology

2014 ◽  
Vol 70 (11) ◽  
pp. 2794-2799 ◽  
Author(s):  
Akira Shinoda ◽  
Yoshikazu Tanaka ◽  
Min Yao ◽  
Isao Tanaka
Keyword(s):  
Drug Discovery ◽  
Drug Screening ◽  
Target Protein ◽  
Protein Crystals ◽  
Anchor Protein ◽  
X Ray ◽  
X Ray Crystallography ◽  
Ligand Screening ◽  
Large Numbers ◽  
Anchoring Protein

X-ray crystallography is an important technique for structure-based drug discovery, mainly because it is the only technique that can reveal whether a ligand binds to the target protein as well as where and how it binds. However, ligand screening by X-ray crystallography involves a crystal-soaking experiment, which is usually performed manually. Thus, the throughput is not satisfactory for screening large numbers of candidate ligands. In this study, a technique to anchor protein crystals to mounting loops by using gel and inkjet technology has been developed; the method allows soaking of the mounted crystals in ligand-containing solution. This new technique may assist in the design of a fully automated drug-screening pipeline.

Protein X-ray Crystallography in Drug Discovery

2005 ◽  
pp. 373-455 ◽  
Author(s):  
Peter Nollert ◽  
Michael D. Feese ◽  
Bart L. Staker ◽  
Hidong Kim
Keyword(s):  
Drug Discovery ◽  
X Ray ◽  
X Ray Crystallography ◽  
Protein X

scholarly journals X-ray crystallography over the past decade for novel drug discovery – where are we heading next?

2015 ◽  
Vol 10 (9) ◽  
pp. 975-989 ◽  
Author(s):  
Heping Zheng ◽  
Katarzyna B Handing ◽  
Matthew D Zimmerman ◽  
Ivan G Shabalin ◽  
Steven C Almo ◽  
...  
Keyword(s):  
Drug Discovery ◽  
X Ray ◽  
X Ray Crystallography ◽  
The Past ◽  
Novel Drug

scholarly journals Identification of novel allosteric inhibitors through fragment-based drug discovery and X-ray crystallography  

2015 ◽  
Vol 71 (a1) ◽  
pp. s38-s38
Author(s):  
Puja Pathuri ◽  
Susanne M. Saalau-Bethell ◽  
Andrew J. Woodhead ◽  
Valerio Berdini ◽  
Maria G. Carr ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Allosteric Inhibitors ◽  
X Ray ◽  
X Ray Crystallography ◽  
Fragment Based Drug Discovery

scholarly journals Contaminant inclusion into protein crystals analyzed by electrospray mass spectrometry and X-ray crystallography

1998 ◽  
Vol 7 (1) ◽  
pp. 185-192 ◽  
Author(s):  
Juan Carlos Fontecilla-Camps ◽  
Frédéric Halgand ◽  
Eric Forest ◽  
Joachim Hirschler
Keyword(s):  
Mass Spectrometry ◽  
Electrospray Mass Spectrometry ◽  
Protein Crystals ◽  
X Ray ◽  
X Ray Crystallography

scholarly journals Small Molecules Bound to Unique Sites in the Target Protein Binding Cleft of Calcium-Bound S100B As Characterized by Nuclear Magnetic Resonance and X-ray Crystallography

Biochemistry ◽  
2009 ◽  
Vol 48 (26) ◽  
pp. 6202-6212 ◽  
Author(s):  
Thomas H. Charpentier ◽  
Paul T. Wilder ◽  
Melissa A. Liriano ◽  
Kristen M. Varney ◽  
Shijun Zhong ◽  
...  
Keyword(s):  
Nuclear Magnetic Resonance ◽  
Magnetic Resonance ◽  
Protein Binding ◽  
Small Molecules ◽  
Target Protein ◽  
X Ray ◽  
X Ray Crystallography ◽  
Binding Cleft ◽  
Nuclear Magnetic

scholarly journals Cocktailed fragment screening by X-ray crystallography of the antibacterial target undecaprenyl pyrophosphate synthase from Acinetobacter baumannii

2020 ◽  
Vol 76 (1) ◽  
pp. 40-46
Author(s):  
James H. Thorpe ◽  
Ian D. Wall ◽  
Robert H. Sinnamon ◽  
Amy N. Taylor ◽  
Robert A. Stavenger
Keyword(s):  
Drug Discovery ◽  
Acinetobacter Baumannii ◽  
Structural Data ◽  
X Ray ◽  
Traditional Medicines ◽  
X Ray Crystallography ◽  
Fragment Screening ◽  
Binding Pockets ◽  
Antibacterial Target ◽  
Robustness Check

Direct soaking of protein crystals with small-molecule fragments grouped into complementary clusters is a useful technique when assessing the potential of a new crystal system to support structure-guided drug discovery. It provides a robustness check prior to any extensive crystal screening, a double check for assay binding cutoffs and structural data for binding pockets that may or may not be picked out in assay measurements. The structural output from this technique for three novel fragment molecules identified to bind to the antibacterial target Acinetobacter baumannii undecaprenyl pyrophosphate synthase are reported, and the different physicochemical requirements of a successful antibiotic are compared with traditional medicines.

scholarly journals Protein X-ray Crystallography and Drug Discovery

Molecules ◽  
2020 ◽  
Vol 25 (5) ◽  
pp. 1030 ◽  
Author(s):  
Laurent Maveyraud ◽  
Lionel Mourey
Keyword(s):  
Drug Discovery ◽  
Structural Information ◽  
Discovery Process ◽  
Drug Discovery Process ◽  
X Ray ◽  
Drug Candidates ◽  
X Ray Crystallography ◽  
Compound Libraries ◽  
Fragment Library ◽  
Invaluable Tool

With the advent of structural biology in the drug discovery process, medicinal chemists gained the opportunity to use detailed structural information in order to progress screening hits into leads or drug candidates. X-ray crystallography has proven to be an invaluable tool in this respect, as it is able to provide exquisitely comprehensive structural information about the interaction of a ligand with a pharmacological target. As fragment-based drug discovery emerged in the recent years, X-ray crystallography has also become a powerful screening technology, able to provide structural information on complexes involving low-molecular weight compounds, despite weak binding affinities. Given the low numbers of compounds needed in a fragment library, compared to the hundreds of thousand usually present in drug-like compound libraries, it now becomes feasible to screen a whole fragment library using X-ray crystallography, providing a wealth of structural details that will fuel the fragment to drug process. Here, we review theoretical and practical aspects as well as the pros and cons of using X-ray crystallography in the drug discovery process.

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