Peptide therapeutics may pave the way for addressing unmet medical needs
Macrocyclic peptides are a diverse family of molecules with a stabilizing ring architecture. These molecules are distinguished from traditional classes of therapeutics by their capacity to disrupt intracellular protein-protein interactions drug targets. Importantly, these targets have traditionally been cast as “undruggable” due to their lack of obvious binding sites for small molecules and their residence inside cells, a location that shields them from antibody-based therapies. The promise of macrocyclic peptides opens up new opportunities to address a range of human diseases such as cancer, cardiovascular and metabolic diseases. Indeed, given their medical potential, peptide therapeutics are on the rise, with the global market expected to grow to US$23.7 billion by 2020.
While macrocyclic peptides offer therapeutic advantages over traditional approaches, their medical potential is currently limited by their marginal ability to penetrate into cells to reach their respective biological drug targets. Accordingly, scientists from MSD (known as Merck & Co., Inc., in the US and Canada)as well as Singapore’s Agency for Science, Technology and Research (A*STAR) Bioinformatics Institute (BII), Institute of Chemical and Engineering Sciences (ICES), Institute of Molecular and Cell Biology (IMCB) and the p53 Lab have formed a two-year collaboration aimed at improving cellular delivery of macrocyclic peptides.
The collaboration aims to uncover the chemical and biophysical properties that influence peptide penetration into cells, as well as to explore the use of smart delivery systems that leverage natural cell entry mechanisms. It will combine MSD’s experience and expertise in drug discovery including medicinal chemistry, pharmacology, pharmacokinetics, and molecular modelling with A*STAR’s research capabilities in multiple areas such as protein peptide interactions, bioinformatics, chemistry and membrane trafficking to establish compound design principles that will help unlock the full therapeutic potential of macrocyclic peptides.
Macrocyclic peptides may hold the key to bridging the gap between the two existing traditional therapeutic strategies – antibodies and small molecules. Biologics like antibodies are too large to enter cells, while small molecules that are able to diffuse into cells are not specific enough in their recognition of targets to be able to effectively target protein-protein interactions.
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