I hope that you are all enjoying the start of your summer; in the UK, we are having a sportsfest, although our participation in the World Cup is at an end, we can live with some expectations that British participation in Wimbledon is likely to be a more extensive experience. Only one comment, then we can get back on to the much more important topic of Science: what is the difference between the England football team and a teabag? A teabag stays in the cup longer.

This month’s newsletter deals with aspects of the use of peptides as therapeutics and their broader use in pharmaceutical research. The first article:  “Future directions for peptide therapeutics development” by Allan A. Kaspar and Janice M. Reichert. They discuss how the expansion in research and development in peptide therapeutics during the late 1990s and early 2000s has led to a robust and significant pipeline, likely to deliver a steady stream of innovative drugs for the rest of this decade and beyond. The current pipeline, with respect to therapeutic areas and targets, is reviewed as are areas for future innovative development, such as constrained peptides and the potentially hot area of peptide-drug conjugates. 

Following on from this excellent article is the very recently published article: “Immunosuppressive peptides and their therapeutic applications” by Kathrin Thell, Roland Hellinger, Gernot Schabbauer and Christian W. Gruber. This article overviews how the immune system detects and evades exogenous threats to the body. The inability to control and regulate this system will, almost inevitably, lead to autoimmunity and related diseases. The autoimmune state is often associated and driven by problematic T-cell signaling and although several drugs are available to dampen the effects of the over-enthusiastic T-lymphocyte response, they have issues with respect to adverse side effect profiles. In this respect, ribosomally-synthesised peptides are attracting great attention as potential replacements for current therapies as a result of their much-improved selectivity and toxicity profiles. In particular, the authors discuss plant cyclotides, which benefit from their improved stability and potential as oral therapeutics.

Finally, the article by Maryam Hamzeh-Mivehroud, Ali Akbar Alizadeh, Michael B. Morris, W. Bret Church and Siavoush Dastmalchi deals with technology important for discovering and developing pipelines of therapeutic peptides and peptidomimetics. This technology is familiar to most of our readers; however, in their paper:  “Phage display as a technology delivering on the promise of peptide drug discovery” they outline the ‘mechanics’ of the technique and how it can be tweaked to produce subtle improvements and approaches to the discovery of peptide therapeutics. One particular interesting approach that they address is the potential to use the phage particle itself as a drug delivery device that can be targeted to a particular pathogen or cell type. This is an essential read for those with an interest in phage display and need bringing up-to-date on the cutting edge of this technology as it relates to current drug discovery.

I hope that these 3 articles will provide a useful guide to the discovery and development of therapeutic peptides and the impact that they are likely to have over the next decade. Moreover, I expect that after reading these you will be optimistic that this class of molecules can continue to have a great impact of the treatment of disease well into the future. 

Steve Carney was born in Liverpool, England and studied Biochemistry at Liverpool University, obtaining a BSc.(Hons) and then read for a PhD on the Biochemistry and Pathology of Connective Tissue Diseases in Manchester University, in the Departments of Medical Biochemistry and Histopathology. On completion of his PhD he moved to the Kennedy Institute of Rheumatology, London, where he worked with Professor Helen Muir FRS and Professor Tim Hardingham, on the biochemistry of experimental Osteoarthritis. He joined Eli Lilly and Co. and held a number of positions in Biology R&D, initially in the Connective Tissue Department, but latterly in the Neuroscience Department. He left Lilly to take up his present position as Managing Editor, Drug Discovery Today, at Elsevier. He has authored over 40 peer-reviewed articles, written several book chapters and has held a number of patents.