I’m sure that I don’t need to tell anyone how the nature of biologically-active molecules and drugs has changed over the last 15 or so years.  Where once the small organic molecule was king, now their throne is challenged by ever more selective biological therapies. Such approaches have not been without their problems, but their benefits are beyond doubt. In this newsletter, I’ve selected a mixed bag of articles to outline some important developments in various fields. Clearly there is a massive interest in peptides, evidenced by a recent article in Drug Discovery Today from Keld Fosgerau and Torsten Hoffmann  entitled “Peptide therapeutics: current status and future directions” from January 2015 which has consistently been our most downloaded and cited (264 to date) of the last 2 years. See the associated download with this editorial, should you wish to read this. The first of our articles in this newsletter hopefully builds upon this interest – I hope that you find it instructive. Our other papers deal with potential uses of natural products as potential lead compounds and, finally how biological molecules might be able to synergize with small organic compounds in therapy by using them to enhance absorption characteristics when, previously such compounds with poor availability may have been abandoned.

The first article in this month’s offering is entitled: “Stapled peptide design: principles and roles of computation”, by Yaw Sing Tan, David P. Lane and Chandra S. Verma. In this article, the authors discuss how stapling can stabilize the α helical structure of peptides. Such stable “stapled” peptides are highly capable of binding to protein sites involved in protein-protein binding and, hence, can represent useful inhibitors of such interactions. In the article, they outline modern stapled peptide design and the use of computational methods and how such approaches can throw light on the mode of action of stapled peptide binding.

The second featured article is by Salvatore Genovese, Serena Fiorito, Vito Alessandro Taddeo and Francesco Epifano of the Department of Pharmacy, University G. d’Annunzio of Chieti-Pescara, Chieti Scalo (CH), Italy and is entitled: “Recent developments in the pharmacology of prenylated xanthones”. The authors outline the significance of prenylated xanthones, common metabolites in plants. The article reviews the structures from a variety of plant species and their potential as therapeutic agents. They have a wide range of activities, from PDE5 inhibitors to cytotoxic agents with the potential of representing oncolytic lead compounds.

Finally, is the article “Current progress in a second-generation claudin binder, anti-claudin antibody, for clinical applications” from Yosuke Hashimoto, Kiyohito Yagi and Masuo Kondoh of the Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka 565-0871, Japan. The article describes how claudins (a broad family of molecules responsible for maintaining the polarity of cells and sealing the junctions between them). Disruption or deregulation of this class of molecule is frequently associated with pathologies such as inflammation and oncogenesis. They propose that disruption of their biological interactions may represent a useful target for enhancing drug absorption of existing (or new) molecules. Currently, this is most efficiently performed using monoclonal antibodies, but the authors describe some of the issues that have historically beset this approach and outline the strategies behind the design and development of more modern therapeutic antibodies.

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. Currently, he also holds an honorary lectureship in Drug Discovery at the University of Surrey, UK. He has authored over 50 articles in peer-reviewed journals, written several book chapters and has held a number of patents.