New Developments in the Field of Protein and Metabolism Assays Aimed at Drug Discovery Processes
Pp. 55-86 (32)
Kothandaraman Narasimhan, Ponnusamy Sukumar and Mahesh Choolani
The advent of new high-throughput proteomic and metabolic assays using mass spectrometry (MS) has significantly benefited drug discovery process. This process is accelerated with the miniaturization of detection devises (nanotechnology and biosensors) to carry out rapid and effective screening. Using proteomics (protein arrays) it is possible to globally investigate the molecular basis of disease, drug action leading to drug development. Similarly metabolic assays for nutritional status, expanded neonatal screening through tandem MS could swift through several thousand data points associated with a particular disease (either proteins/peptides or metabolites) in a short span of few minutes and come up with highly sensitive and accurate diagnosis. Nanobiotechnology raises fascinating possibilities for new analytical array based assays (receptor-ligand binding, DNA-DNA hybridization, or both) and microanalytic separations, each of which will be mentioned here with respect to their ability to affect the drug discovery processes. Molecular profiling by DNA microarray technology has made significant contributions to the understanding of molecular targets for diseases such as cancer. One of the challenges is how to efficiently utilize the accumulated research data to develop new diagnostic and/or prognostic markers and therapeutic targets. Proteomics based disease therapeutic research involves high-throughput protein structure determination (e.g. structural biology of protein tyrosine kinases (PTKs). These processes involve conventional antibody based arrays as well as targets identified using structural biology for narrowing down targets for drug delivery. Drug discovery processes aimed at generating inhibitors for the treatment of malignancies are believed to be dependent on the gain of function of specific PTKs. Current research include Src as a target for pharmaceutical intervention, JAK kinases in leukemias/lymphomas, and phosphoproteomics. The following areas mentioned above will form the key focus of this chapter.
Diagnostic Biomarker Discovery Laboratory, Department of Obstetrics and Gynaecology, National University Hospital, 5 Lower Kent Ridge Road, Singapore 119074.