Sometimes things come as great surprises. Well, I got a huge surprise when I looked at some of Drug Discovery Today’s usage data over the last few years. I always imagine that all of our articles will be well-cited, as we try to encourage only the best authors writing on the hottest topics, but the article by Fosgerau.and Hoffmann, entitled: “Peptide therapeutics: Current status and future directions” was cited way above my highest expectations. Currently, it has been cited 401 times since it was published in January 2015. A little old, therefore, to be included in this newsletter, but was a wake up call for me with respect to the continuing interest and popularity of peptides as potential drug molecules and as part of the drug discovery process. It is my pleasure, therefore, to highlight some of the more recent articles from Drug Discovery Today that deal with peptides as drugs, or approaches to novel design of such molecular entities.
The first article in this month’s offering is entitled: “Interfering peptides targeting protein–protein interactions: the next generation of drugs?”, by Heriberto Bruzzoni-Giovanelli, Valerie Alezra, Nicolas Wolff, Chang-Zhi Dong, Pierre Tuffery and Angelita Rebollo of various institutes from Paris, France. As is clear from the title, this article discusses the role that peptides might be able to play in disrupting protein-protein interactions to achieve pharmacological benefit. As a result of novel approaches to administration and strategies to enhance the stability of circulating peptides and their intracellular uptake, peptide therapies are experiencing an upsurge in interest in their potential as new drugs. Such peptides are important in being one of the few agents that are likely to be able to disrupt the interaction of large proteins, as small molecular weight compounds (around 500 Da) are most likely to find it thermodynamically impossible to interfere with the large negative Gibbs Free Energy of interaction of such large molecules. As biology identifies more and more protein-protein interactions that might be responsible for pathology, such interfering peptides are likely to become ever more important as pharmacological tools, or potential drug entities.
The second featured article is by Nicolau B. da Cunha, Nicole B. Cobacho, Juliane F.C. Viana, Loiane A. Lima, Kamila B.O. Sampaio, Stephan S.M. Dohms, Arthur C.R. Ferreira, César de la Fuente-Núñez, Fabrício F. Costa, Octávio L. Franco and Simoni C. Dias of various institutes in Brazil and Cambridge MA, USA. It is entitled: “The next generation of antimicrobial peptides (AMPs) as molecular therapeutic tools for the treatment of diseases with social and economic impacts”. In this article, the authors discuss the current state of play in the development of natural peptides as potential drugs and advances in the design and biosynthesis of potentially important therapeutic peptides. The focus of the article is on the development of antimicrobial peptides, a field that is becoming more and more important due to the increase in drug resistance in bacteria as we move away from the Golden Age of antibiotic therapy.
Last, but by no means least, in this month’s offering is: “Stapled peptide design: principles and roles of computation” from Yaw Sing Tan, David P. Lane and Chandra S. Verma from various institutions in Singapore. This article presents a foil for our first offering, in that it deals with the design of stapled peptides. Such peptides can be engineered to form α helices, which stabilizes their structure and can improve many of the issues associated with their in vivo stability and vastly improves their ability to be able to destabilize protein-protein interactions. The authors go on to discuss those computational methodologies that have been key to the design of stapled peptides and their contribution to the field. Furthermore, they speculate that such computational approaches may provide an insight into the (currently unclear) mode of action of stapled peptides.
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.