We report on an innovative ligand discovery strategy based on protein NMR-based screening of a combinatorial library of ~125,000 compounds that was arranged in 96 distinct mixtures. Using sensitive solution protein NMR spectroscopy and chemical perturbation-based screening followed by an iterative synthesis, deconvolutions, and optimization strategy, we demonstrate that the approach could be useful in the identification of initial binding molecules for difficult drug targets, such as those...
NMR quality control of fragment libraries for screening
NMR quality control of fragment libraries for screening
Abstract
Fragment-based screening has evolved as a remarkable approach within the drug discovery process both in the industry and academia. Fragment screening has become a more structure-based approach to inhibitor development, but also towards development of pathway-specific clinical probes. However, it is often witnessed that the availability, immediate and long-term, of a high quality fragment-screening library is still beyond the reach of most academic laboratories. Within iNEXT...
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06-13-2020 05:51 PM
[NMR paper] Introducing the CSP Analyzer: A novel Machine Learning-based application for automated analysis of two-dimensional NMR spectra in NMR fragment-based screening.
Introducing the CSP Analyzer: A novel Machine Learning-based application for automated analysis of two-dimensional NMR spectra in NMR fragment-based screening.
Related Articles Introducing the CSP Analyzer: A novel Machine Learning-based application for automated analysis of two-dimensional NMR spectra in NMR fragment-based screening.
Comput Struct Biotechnol J. 2020;18:603-611
Authors: Fino R, Byrne R, Softley CA, Sattler M, Schneider G, Popowicz GM
Abstract
NMR-based screening, especially fragment-based drug discovery is a...
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04-09-2020 05:35 AM
[NMR paper] Application of Dirichlet process mixture model to the identification of spin systems in protein NMR spectra.
Application of Dirichlet process mixture model to the identification of spin systems in protein NMR spectra.
Related Articles Application of Dirichlet process mixture model to the identification of spin systems in protein NMR spectra.
J Biomol NMR. 2018 May 18;:
Authors: Klukowski P, Augoff M, Zamorski M, Gonczarek A, Walczak MJ
Abstract
Analysis of structure, function and interactions of proteins by NMR spectroscopy usually requires the assignment of resonances to the corresponding nuclei in protein. This task, although...
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05-20-2018 06:02 PM
Application of Dirichlet process mixture model to the identification of spin systems in protein NMR spectra
Application of Dirichlet process mixture model to the identification of spin systems in protein NMR spectra
Abstract
Analysis of structure, function and interactions of proteins by NMR spectroscopy usually requires the assignment of resonances to the corresponding nuclei in protein. This task, although automated by methods such as FLYA or PINE, is still frequently performed manually. To facilitate the manual sequence-specific chemical shift assignment of complex proteins, we propose a method based on Dirichlet process mixture model (DPMM) that...
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05-19-2018 05:30 AM
[NMR paper] Toxic responses of Perna viridis hepatopancreas exposed to DDT, benzo(a)pyrene and their mixture uncovered by iTRAQ-based proteomics and NMR-based metabolomics.
Toxic responses of Perna viridis hepatopancreas exposed to DDT, benzo(a)pyrene and their mixture uncovered by iTRAQ-based proteomics and NMR-based metabolomics.
Toxic responses of Perna viridis hepatopancreas exposed to DDT, benzo(a)pyrene and their mixture uncovered by iTRAQ-based proteomics and NMR-based metabolomics.
Aquat Toxicol. 2017 Sep 11;192:48-57
Authors: Song Q, Zhou H, Han Q, Diao X
Abstract
Dichlorodiphenyltrichloroethane (DDT) and benzo(a)pyrene (BaP) are environmental estrogens (EEs) that are ubiquitous in the...
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09-18-2017 10:41 AM
[NMR paper] Acceleration of protein backbone NMR assignment by combinatorial labeling: Application to a small molecule binding study.
Acceleration of protein backbone NMR assignment by combinatorial labeling: Application to a small molecule binding study.
Acceleration of protein backbone NMR assignment by combinatorial labeling: Application to a small molecule binding study.
Biopolymers. 2016 Dec 30;:
Authors: Hein C, Löhr F, Schwarz D, Dötsch V
Abstract
Selective labeling with stable isotopes has long been recognized as a valuable tool in protein NMR to alleviate signal overlap and sensitivity limitations. In this study, combinatorial (15) N-, (13) C(?) -,...
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12-31-2016 12:18 PM
[U. of Ottawa NMR Facility Blog] Cross Polarization Based Mixture Resolution in Solids
Cross Polarization Based Mixture Resolution in Solids
One of the most common techniques used to collect solid-state NMR data for spin I = ½ nuclides is a combination of cross polarization (CP) and magic angle spinning (MAS). CPMAS provides high sensitivity from the CP and high chemical shift resolution from the MAS. Furthermore, the scan repetition rate depends on the shorter relaxation time of the protons rather than the longer relaxation time of the spin I = ½ nuclide therefore, more scans can be collected per unit time. It must be remembered however, that the success of the CP...
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03-31-2015 07:17 PM
[NMR paper] HTS by NMR of Combinatorial Libraries: A Fragment-Based Approach to Ligand Discovery.
HTS by NMR of Combinatorial Libraries: A Fragment-Based Approach to Ligand Discovery.
http://www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--linkinghub.elsevier.com-ihub-images-cellhub.gif Related Articles HTS by NMR of Combinatorial Libraries: A Fragment-Based Approach to Ligand Discovery.
Chem Biol. 2013 Jan 24;20(1):19-33
Authors: Wu B, Zhang Z, Noberini R, Barile E, Giulianotti M, Pinilla C, Houghten RA, Pasquale EB, Pellecchia M
Abstract
Fragment-based ligand design (FBLD) approaches have become more widely used in drug discovery...
Mixture-Based Screening of Focused Combinatorial Libraries by NMR: Application to the Antiapoptotic Protein hMcl-1
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