Journal
CURRENT TOPICS IN MEDICINAL CHEMISTRY
Volume 9, Issue 18, Pages 1725-1735Publisher
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/156802609790102392
Keywords
SPR; biosensor; fragment-based lead discovery; interactions; kinetics; affinity; screening
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The transition from high throughput screening of collections of drug-like compounds to screening of fragment libraries via lower throughput methods with high sensitivity has revolutionized early drug discovery. It is highlighting the need for sensitive biophysical techniques for interaction analysis rather than high throughput methods. Biosensors with SPR detection are well suited for this novel scenario. In less than 20 years the technique has been launched, established and become a highly informative method for a variety of applications in drug discovery. It is no longer limited to the detection of proteins or other high molecular weight analytes, but the detection of weakly interacting fragments is now feasible. This paper discusses the theoretical and experimental limitations for such applications and reviews a number of successful studies in the area of fragment-based lead discovery that have recently been published. It can be anticipated that the evolution of this young technique will be significantly influenced by the requirements for efficient fragment-based lead discovery.
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