title: Developments in SPR Fragment Screening.
abstract: BACKGROUND
  Fragment-based approaches have played an increasing role alongside high-throughput screening in drug discovery for 15 years. The label-free biosensor technology based on surface plasmon resonance (SPR) is now sensitive and informative enough to serve during primary screens and validation steps.
  
  
  METHODS
  In this review, the authors discuss the role of SPR in fragment screening. After a brief description of the underlying principles of the technique and main device developments, they evaluate the advantages and adaptations of SPR for fragment-based drug discovery. SPR can also be applied to challenging targets such as membrane receptors and enzymes.
  
  
  CONCLUSIONS
  The high-level of immobilization of the protein target and its stability are key points for a relevant screening that can be optimized using oriented immobilized proteins and regenerable sensors. Furthermore, to decrease the rate of false negatives, a selectivity test may be performed in parallel on the main target bearing the binding site mutated or blocked with a low-off-rate ligand. Fragment-based drug design, integrated in a rational workflow led by SPR, will thus have a predominant role for the next wave of drug discovery which could be greatly enhanced by new improvements in SPR devices.
authors.affiliation: a Institut des Biomolécules Max Mousseron (IBMM), UMR 5247 , Université de Montpellier, CNRS, ENSCM , Montpellier Cedex 5, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Chavanieu
authors.affiliation: b IRCM , Institut de Recherche en Cancérologie de Montpellier , Montpellier , France.|c INSERM, U1194 , Université Montpellier , Montpellier , France.|d ICM , Institut Régional du Cancer , Montpellier , France.
authors.forename: Martine
authors.initials: M
authors.lastname: Pugnière
mesh_terms: D018360:Crystallography, X-Ray; D055808:Drug Discovery; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D020349:Surface Plasmon Resonance
keywords: Fragment-based drug design; fragment screening; molecular interaction; surface plasmon resonance