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Since the introduction of insulin almost a century ago, more than 80 peptide drugs have been approved for a wide range of diseases. This Perspective summarizes trends in peptide drug discovery, emphasizing lessons from earlier approaches as well as emerging strategies such as integrated venomics and peptide-display libraries. It also analyses the remaining challenges and the pharmaceutical landscape in which peptide drugs are particularly valuable.
Natural products have historically made a major contribution to pharmacotherapy, but also present challenges for drug discovery, such as technical barriers to screening, isolation, characterization and optimization. This Review discusses recent technological developments — including improved analytical tools, genome mining and engineering strategies, and microbial culturing advances — that are enabling a revitalization of natural product-based drug discovery.
Protein lysine methylation is an important post-translational modification of histone and non-histone proteins. In this Review, Gozani and colleagues discuss the role of protein lysine methyltransferases, the ‘writers’ of protein lysine methylation, in a range of diseases, and the progress and potential of targeting these enzymes therapeutically. They also consider the biology of lysine methyltransferases beyond epigenetic regulation as emerging targets for drug discovery.
Numerous proteins and lipids are covered in glycans, which affects the way these molecules interact. In this Review, Smith and Bertozzi discuss therapies targeting proteins that recognize glycosylation, namely the selectins and Siglecs, as well as glycan-targeted antibodies that have entered the clinic or are in development. They provide their perspectives on the future of glycobiology.
Misconceptions about translation — defined as the process of turning observations in the laboratory, clinic and community into interventions that improve the health of individuals — hinder efforts to close gaps and address challenges related to the translational process. This article highlights some misconceptions with the aim of improving understanding and advancing solutions.