Developments in SPR Fragment Screening. (3rd May 2016)

• Record Type: Journal Article
• Authors: Chavanieu, Alain; Pugnière, Martine
• Is Part Of: Expert opinion on drug discovery. Volume 11:Number 5(2016:May)
• Page Start: 489
• Page End: 499
• Publication Date: 2016-05-03
• Subjects: Fragment-based drug design -- fragment screening -- molecular interaction -- surface plasmon resonance; 615.1
• DOI: 10.1517/17460441.2016.1160888
• Languages: English
• ISSNs: 1746-0441

Abstract

ABSTRACT: Introduction : 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. Areas covered : 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. Expert opinion : 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.