uri physics colloquium

Turning Intrinsically Disordered Proteins into Drug Targets – How is that Possible? 

Wolfgang Peti, Ph. D
Department of Molecular Pharmacology, Physiology & Biotechnology; Department of Chemistry; Department of Molecular Biology, Cell Biology and Biochemistry; Brown University, Providence, RI

abstract

Protein phosphatases are efficient enzymes that are essential regulators of a large number of key biological functions. Interestingly, only very little is known about their regulation at an atomic level. Recent advances have shown that they have explicit specificity for their substrates. Furthermore, as of their importance for a plethora of biological function, it is of no surprise that they are seen as critical drug targets. Different methods have been used for drug design: from active site to allosteric site to protein:protein interaction inhibitors. However, only the protein:protein interaction inhibitors (cyclosporin A and FK-506 for PP2B/Calcineurin) have been successfully used in the clinic.

Here we describe a new approach that targets – in a highly specific manner – the IDP region of the tyrosine phosphatase PTP1B. However, improvement of the compound is limited to experimental methods as computational drug design for IDP regions is currently impossible.