Abstract

The concept of tethering has become enormously popular in the past few years which facilitated binding of protein targets with smaller molecules or fragments in order to achieve successful leads and their optimization. The concept behind tethering is additive binding to yield a high affinity lead molecule which involves binding to protein, chemical modification and then its optimization to get a lead structure. Three types of tethering studies are Co-operative tethering, Extended tethering and Breakaway tethering which are studied with reference to various enzymes like Caspase3, Interlukin-2, Protein Tyrosine Phosphatase 1B etc. The need for rapid target identification and evaluation is resulting in an increase in pressure on an already strained pharmaceutical industry. As a first step toward target validation, tool compounds are invaluable in assessing the potential of drug targets. This review attempts to summarize how Tethering can rapidly identify tool compounds for a difficult target and provide effective hits. Although Tethering was initially developed to provide high-quality starting points for well-validated, highly characterized targets, the use of IL-2 as a model system proves its potential in early target assessment.