TY  - JOUR
A1  - Sreeramulu, Sridhar
A1  - Richter, Christian
A1  - Kühn, Till
A1  - Azzaoui, Kamal
A1  - Blommers, Marcel Jules José
A1  - Del Conte, Rebecca
A1  - Fragai, Marco
A1  - Trieloff, Nils
A1  - Schmieder, Peter
A1  - Nazaré, Marc
A1  - Specker, Edgar
A1  - Ivanov, Vladimir
A1  - Oschkinat, Hartmut
A1  - Banci, Lucia
A1  - Schwalbe, Harald
T1  - NMR quality control of fragment libraries for screening
T2  - Journal of biomolecular NMR
N2  - 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 (Infrastructure for NMR, EM and X-rays for Translational research), a EU-funded Horizon 2020 program, a collection of 782 fragments were assembled utilizing the concept of “poised fragments” with the aim to facilitate downstream synthesis of ligands with high affinity by fragment ligation. Herein, we describe the analytical procedure to assess the quality of this purchased and assembled fragment library by NMR spectroscopy. This quality assessment requires buffer solubility screening, comparison with LC/MS quality control and is supported by state-of-the-art software for high throughput data acquisition and on-the-fly data analysis. Results from the analysis of the library are presented as a prototype of fragment progression through the quality control process.
KW  - Drug discovery
KW  - FBDD
KW  - Ligands
KW  - Fragment
KW  - Quality control
KW  - Solubility
KW  - NMR
Y1  - 2020
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/63756
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-637565
SN  - 1573-5001
N1  - Open Access funding provided by Projekt DEAL. This work has been supported by iNEXT and iNEXT-discovery, Grant Numbers 653706 and 871037, funded by the Horizon 2020 program of the European Commission. This research was financially supported by the German Cancer Consortium (DKTK) and DFG (SFB807).
VL  - 74
IS  - 10-11
SP  - 555
EP  - 563
PB  - Springer Science + Business Media B.V
CY  - Dordrecht [u.a.]
ER  -