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Peptide therapeutics will open up new opportunities to address unmet medical needs

Singapore – Singapore’s Agency for Science, Technology and Research (A*STAR) and MSD (known as Merck & Co., Inc., in U.S.A. and Canada) have formed a two-year collaboration aimed at improving cellular delivery of macrocyclic peptides, a class of molecules that can potentially access therapeutic strategies that have been refractory to traditional approaches.

Macrocyclic peptides are a diverse family of molecules with a stabilizing ring architecture. What distinguishes these molecules from traditional classes of therapeutics is their capacity to disrupt intracellular protein-protein interactions drug targets. Importantly, these targets have traditionally been cast as ‘undruggable’1 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. Accordingly, 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. Globally, the market for peptide therapeutics is expected to grow to US$23.7 billion by 2020.[1]

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, this collaboration, which involves scientists from MSD as well as A*STAR’s Bioinformatics Institute (BII), Institute of Chemical and Engineering Sciences (ICES), Institute of Molecular and Cell Biology (IMCB) and the p53 Lab, 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. The collaboration 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.

Prof. Sir David Lane, Chief Scientist of A*STAR and Director of the p53 lab, said, “Therapeutic peptide research is gaining momentum and it is exciting to see multiple research institutes from A*STAR working together with a global leader in the pharmaceutical industry to build capabilities in this area. By collaborating with MSD, we are confident that we will be able to accelerate innovation and contribute to the growing peptide therapeutics market and improve treatments for a whole range of diseases.”

Dr. Rich Tillyer, Senior Vice President, Chemistry, of MSD said, “We believe that by combining expertise with A*STAR, we will make significant advances in our ability to apply peptide therapeutics to highly validated intracellular targets that have historically been out of reach. In that regard, this collaboration represents an important step towards novel medicines that will save and improve lives.”

[1]Source: http://www.transparencymarketresearch.com/peptide-therapeutics-market.html

IMAGE

Figure 1 (Provided by Dr Chandra Verma, BII, A*STAR)

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.

Figure 1 demonstrates how a macrocyclic peptide (in pink and cyan) is able to inhibit protein-protein interactions by binding to the intended target protein (in surface) inside the cell.


For media queries and clarifications, please contact:

A*STAR:
Ms Kueh Xiu Qing
Senior Officer, Corporate Communications
Agency for Science, Technology and Research
Tel: +65 6826 7654
Email: kueh_xiu_qing@scei.a-star.edu.sg

MSD:
Mr Ian McConnell
Executive Director, Global Communications
Merck Sharp & Dohme Corp.
Email: Ian_McConnell@merck.com

About the Agency for Science, Technology and Research (A*STAR)

The Agency for Science, Technology and Research (A*STAR) is Singapore's lead public sector agency that spearheads economic oriented research to advance scientific discovery and develop innovative technology. Through open innovation, we collaborate with our partners in both the public and private sectors to benefit society.

As a Science and Technology Organisation, A*STAR bridges the gap between academia and industry. Our research creates economic growth and jobs for Singapore, and enhances lives by contributing to societal benefits such as improving outcomes in healthcare, urban living, and sustainability.

We play a key role in nurturing and developing a diversity of talent and leaders in our Agency and Research Institutes, the wider research community and industry. A*STAR oversees 18 biomedical sciences and physical sciences and engineering research entities primarily located in Biopolis and Fusionopolis.

For more information on A*STAR, please visit www.a-star.edu.sg.

About MSD

For 125 years, MSD has been a global health care leader working to help the world be well. MSD is a trade name of Merck & Co., Inc., Kenilworth, N.J., USA. Through our prescription medicines, vaccines, biologic therapies and animal health products, we work with customers and operate in more than 140 countries to deliver innovative health solutions. We also demonstrate our commitment to increasing access to health care through far-reaching policies, programs and partnerships.

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