Hello Ron, the 12th Peptoid summit is just around the corner. From August 7-9, it will bring together scientific experts from around the world to explore new frontiers in bio-inspired polymer research and development. I'm eager to hear your thoughts on what you consider the most exciting new development this year.
Hi Dominik. Thanks! I’d say one of the most exciting things happening in our field, is the emergence of several peptoids of commercial importance being developed in industry. Several startups and young companies have found compounds with impressive biological activity, and are advancing them from research into development. For example, a peptoid that binds to growing ice crystals and softens their shape, has been developed to minimize tissue damage in organ transplants. A different family of peptoids with broad-spectrum anti-bacterial and antifungal activity, are being developed to fight chronic infections caused by complex microbial communities. And a third class of peptoids can help package mRNA into well-behaved lipid nanoparticles, enabling their use as mRNA vaccines and therapeutics. It’s exciting to see how low molecular weight, sequence-defined peptoids, are beginning to make an impact in these very different fields: organ preservation, therapeutics, and drug delivery.
Through these industrial efforts, peptoids are now being produced and purified on the multi-gram to kg scale. GMP peptoid manufacturing by solid-phase synthesis is currently underway and proving to be feasible for many applications. A long-standing challenge for our field has been to demonstrate the financial viability of a commercial peptoid product, and major steps toward that have now been achieved.
In other areas, the field of functional peptoid nanomaterials continues to thrive, where peptoid crystal lattices have been decorated with novel functional domains to achieve an impressive array of properties, including catalysis and molecular recognition. There’s also been a sharp increase in the development of computational tools to study peptoids, both to predict new functional peptoid structures, and to analyze and learn from large datasets.
There are many more exciting developments – spanning chemistry, biology, polymers, nanoscience and computation – that will be shared at the Summit. We hope anyone with an interest in the area will come join us at the meeting to see the latest developments in our field (and to pick up a Summit frisbee)!
Peptoids have become a well-established modality for developing novel drugs and materials. What do you believe were the key breakthroughs that paved the way for the success of peptoids?
I’d say the key breakthrough happened 32 years ago: when we discovered the submonomer solid-phase peptoid synthesis method*. It allowed us to make sequence-defined biomimetic oligomers quickly, cheaply, and in high yield, from a diverse set of readily obtainable building blocks. The coupling chemistry involves two simple synthetic steps, that can be performed in air, at room temperature, using stable reagent solutions. This allowed the entire process to be fully automated, by using custom robotics or standard commercial peptide synthesizers.
The ability to readily produce such an immense universe of chemically diverse peptoid sequences in high yield, really opened the doors of synthetic accessibility. For the first time we could think about synthesizing molecules the size of small proteins, with hundreds of choices at every monomer position! It was quite overwhelming at first.
But this served to sharply advance our field, moving us from “How do we make it?” to “What should we make?”. It was a shift to a much more expansive and imaginative mindset, and enabled people beyond synthetic chemistry to get involved.
Most research groups studying peptoids today use commercial automated peptide synthesizers to make their peptoids. We are indebted to your industry for providing the enabling synthesis technology that is at the very root of our field.
Where do you envision the exciting future of peptoid-based materials and therapeutics taking us?
I think we are entering the age of designability. The peptoid community has established a tremendous body of literature over the past 30 years, and we are beginning to see patterns in what peptoids like to do in terms of their structural preferences, biological activities, self-assembly properties, etc. The modularity of the peptoid structure allows combinatorial exploration and gives us the opportunity to develop a correlation between sequence and structure and function. We hope to one day predictively design and engineer peptoid structure and function with the same precision as can be done today for proteins. I am excited about how artificial intelligence and machine learning can help tackle this problem.
I am also happy to see the continued advancement of bioactive peptoids, across therapeutics, diagnostics and vaccines. It’s exciting to see that funding agencies and industry are willing to invest in bringing the immense promise of peptoids slowly to fruition, in academic, government, and industrial labs across the world.
Thank you for the insightful interview, Ron. We appreciate your time and expertise. To all bio-inspired polymer scientists, don't miss the opportunity to showcase your research and connect with top scientific minds at the 12th Peptoid Summit. Sign up here to secure your place at this premier event from August 7-9 in Berkeley, California. Also, please watch out for the Gyros Protein Technologies booth. We are happy to welcome you there for a deep dive into automated synthesis solutions for this fascinating class of compounds.
*Zuckermann, R. N., Kerr, J. M., Kent, S. B. H., Moos, W. H., Efficient Method for the Preparation of Peptoids [Oligo(N-substituted glycines)] by Submonomer Solid Phase Synthesis. J. Am. Chem. Soc., 114, 10646 (1992).