Protein-Protein Interaction Inhibitors: From Design and Synthesis, Through Biophysics to Cell Permeable Inhibitors

The development of new medicines relies upon the ability of scientists to understand the biological details of a disease and also the way in which new molecular medicines can be designed to either cure the illness or alleviate its symptoms. One very important biological mechanism is the way in which one protein recognises and binds to another protein in order to regulate its function. This functional regulation by protein-protein interactions underpins most of the biological activity in living cells, and yet we do not understand what properties of a protein allow it to bind to another, nor do we understand how to design molecules to prevent or enhance such interactions. Gaining such an understanding would be a huge advance. It is estimated that there are approximately 650,000 types of specific protein-protein interactions in each human cell. This means that there are potentially 650,000 targets for modifying biological function by the use of drugs. Essentially every part of the biological process, and therefore every disease, could in principle be addressed by such drugs. Although the knowledge of how to do this remains beyond our grasp, progress has been made in some parts of the problem, and new ways of looking at the problem have also been developed with others already in development. This research network has the aim of bringing the whole UK community engaged in this type of research together, and in particular connecting the scientists in universities and research institutes with the scientists in biotechnology and pharmaceutical companies to pool their intellectual and technical capabilities. In doing this we have two main aims in mind. Firstly the sharing of knowledge so that everyone has a wider picture of what is now possible and understood and what still needs to be learned and discovered. Secondly the formulation of a UK-wide plan to solve the outstanding problems in this area with the intention of accelerating the development of new drugs for serious illnesses by connecting together progress made by the various research teams across the UK.

Pathways to Impact Summary

UK research councils, charities and industry all invest in research on protein-protein interactions but the many scientific challenges within this field are each, multifaceted, multidisciplinary and interlinked.
The purpose of the network is therefore to increase the impact of the funding already in place and to define a landscape that will assist in helping future funding to have the maximum impact. This means impact both on the field of PPI research and on the ultimate fruition of this research which is the discovery, subsequent development and successful deployment of new drugs to the benefit of public health and the UK economy.
This proposal focuses on a challenge of major relevance to modern day healthcare. Protein-protein interactions represent a target class for molecular therapeutics that far exceeds the chemical and biological space which the scientific community is capable of addressing. This is relevant to a number of end users
(a) The academic community
(b) The pharmaceutical industry
(c) The systems biology community
(d) Clinicians
A specific objective of this call is the development of better links between industry and academia in the area of chemical biology. These end-users will directly benefit from access to the leading academics in the area of PPIs and the opportunity to define the scientific agenda in partnership. At a societal level, we recognize this network call as an opportunity to explore and develop a cultural change within the scientific community - better interaction with users across the entire spectrum of the translational healthcare community.
Beyond new research activity, funding agencies and learned societies will have access to the outputs of the network (e.g. the PPI Roadmap) and this will benefit the entire user community from the academic through to policy makers as a document that influences the future scientific and funding agenda.