Combinatorial Chemistry & High Throughput Screening - Volume 12, Issue 8, 2009

The use of label-free detection technologies in the pharmaceutical and biotechnology industries continues to grow. In addition, the variety of different label-free detection technologies increases year after year, with many new technologies originally developed both in academic and commercial laboratories now reaching the marketplace. The pharmaceutical and biotechnology sectors, particularly high throughput scr Read More

Surface plasmon resonance (SPR) sensors have proven themselves over the last 20 years to be an effective method to study biomolecular binding and kinetics without the use of labeling. More recently, the approach has been adapted to high throughput use with the imaging of SPR-active microarrays. This is an excellent tool for monitoring microarray binding in real-time where the microarray probes and targets can includ Read More

In this review various technologies and approaches for the utilization of mass spectrometry in high throughput analyses are discussed. The use of quadrupole-based mass spectrometry in the screening of chemical libraries against enzymatic targets for the identification of inhibitors and/or activators is highlighted. The RapidFire mass spectrometry system, an integrated on-line solid-phase extraction system interfaced to a tr Read More

This manuscript describes the discovery and characterization of inhibitors of the lipid phosphatase SHIP2, an important target for the treatment of Type 2 diabetes, using the Automated Ligand Identification System. ALIS is an affinity selection-mass spectrometry platform for label-free, high throughput screening of mixture-based combinatorial libraries. We detail the mass-encoded synthesis of a library that yielded NGD-6133 Read More

Isothermal titration calorimetry (ITC) is a label free technique used for direct detection of biological interactions by measurement of the heat given off or taken up during the reaction. In this article we will introduce the ITC technique and review two applications of ITC in drug discovery; small molecule/protein interactions and enzyme kinetics. We will also describe the characteristics of a new miniaturized, ultrasensitive calorim Read More

The analysis of biomolecular interactions is key in the drug development process. Label-free biosensor methods provide information on binding, kinetics, concentration, and the affinity of an interaction. These techniques provide real-time monitoring of interactions between an immobilized ligand (such as a receptor) to an analyte in solution without the use of labels. Advances in biosensor design and detection using BioLayer Read More

Label-free detection methods have played a very significant role in drug design and refinement [1]. They have been used primarily during secondary screening and for in-depth characterization of biomolecular interactions. Misconceptions about the accessibility of these platforms, since they often require specialized training, throughput and robustness in complex media have hampered their adoption in the earliest phase Read More

Drug discovery efforts advance in step with advancements in assay technologies, as new technologies provide new lenses through which biology can be viewed. The novel information gathered results in the better understanding of drug-target interactions leading to better decision making during the drug discovery process. One area of rapid development is within label-free technologies. Label-free technologies offer many Read More

John McCarter is a Principal Scientist in Lead Discovery at Amgen where he leads a group focusing on the discovery and development of small molecule therapeutics for enzyme and cellular targets. Prior to joining Amgen in 2000, John was a Senior Scientist and Project Leader at Axys Pharmaceuticals where he contributed to the cathepsin K program leading to the clinical development (partnered with Merck) of inhibito Read More