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Recombinant Kinase Production and Fragment Screening by NMR Spectroscopy

  • Byeonggu Han
  • Hee-Chul Ahn
Part of the Methods in Molecular Biology book series (MIMB, volume 1360)

Abstract

During the past decade fragment-based drug discovery (FBDD) has rapidly evolved and several drugs or drug candidates developed by FBDD approach are clinically in use or in clinical trials. For example, vemurafenib, a V600E mutated BRAF inhibitor, was developed by utilizing FBDD approach and approved by FDA in 2011. In FBDD, screening of fragments is the starting step for identification of hits and lead generation. Fragment screening usually relies on biophysical techniques by which the protein-bound small molecules can be detected. NMR spectroscopy has been extensively used to study the molecular interaction between the protein and the ligand, and has many advantages in fragment screening over other biophysical techniques. This chapter describes the practical aspects of fragment screening by saturation transfer difference NMR.

Key words

Fragment Fragment-based drug discovery Kinase Optimum solubility screening NMR screening Saturation transfer difference Surface plasmon resonance X-ray crystallography 

Notes

Acknowledgement

This work was supported by the GRRC program of Gyeonggi province [(GRRC-DONGGUK2014-B02), diseasesDevelopment of novel recombinant enzymes and diagnostic platform].

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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.Department of PharmacyDongguk University-SeoulIlsandong-gu, GoyangRepublic of Korea

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