Exploration Science with Dr. Wendy Hartsock and Dr. Diedra Shorty

In this episode of Exploration Science, CEO and Co-founder of Numaferm, Dr. Christian Schwarz, and peptide manufacturing expert, Dr. Alain Scarso, discuss the peptide therapeutics market and dive into the technology of Numaswitch – a transformative biochemical platform to produce peptides, pepteins, and proteins.

In this episode of Exploration Science, Pepticom co-founders, Dr. Immanuel Lerner and Dr. Amit Michaeli, discuss the advantage of employing biocomputational AI software to optimize peptide drug discovery, reduce development risks, and accelerate time to market.

In this episode of Exploration Science, Dr. James Nowick (University of California, Irvine) and Dr. Nick Truex (University of South Carolina) delve into the complexities of designing, synthesizing, and examining biologically significant peptides. They also share fond memories of their time working together in the lab.

In this episode of ExplorationScience, Dr. Jonathan Steckbeck, the founder and CEO of Peptilogics, discusses the company's approach to peptide drug discovery. Tune into this episode to learn how partnering biology with machine learning is guiding the intelligent navigation of peptide chemical space to develop next-generation therapeutics.

In this episode of Exploration Science, Dr. David Shoultz, Chief Operating Officer & Co-Founder of Monod Bio discusses the next generation of clinical diagnostics and how the company is transforming point of care for patients. Tune in and learn how scientists at Monod Bio are driving diagnostic innovation through de novo protein design and deploying lucCage technology. This platform is based on research conducted by Dr. David Baker and scientists at the University of Washington Institute for Protein Design to generate artificial luciferases with optimized size, stability, substrate specificity, and photophysical properties.

In Episode 4 of Exploration Science, Professors Anna Mapp and Ethriam Brammer, alongside Dr. Erin Doherty, discuss the relevance of the GRE standardized test as a method for graduate school admission. They discuss methods they’ve used to assess the effectualness of the GRE, the process of removing the exam from their university admission requirements, and provide advice to those who are seeking to have the GRE removed in the future.

Welcome to Season 2 of Exploration Science! We are so excited about the expanded content and even more excited to introduce our new co-host, Dr. Diedra Shorty!

Tune in Tuesday, 9/27, for Season 2, Episode 1!

In this bonus episode of Exploration Science From the Road, guests Drs. Florence Brunel, Sorina Chiorean, Ingrid Dijkgraaf, and Michael Bertucci recap some of the highlights of the 2022 American Peptide Symposium which took place in Whistler Canada this June.

In part 2 of Exploration Science on the road at the joint French-Belgian Joint Meeting in Port Leucate France, I sat down with Professor Philippe Karoyan and discussed his incredible research efforts as a peptide scientist in France in the early stages of the COVID pandemic, as well as his projects in oncology, and his unique academic lab location within a pharmaceutical company.

2022 brought a special opportunity to bring together the French Group of Peptides and Proteins and the Belgian Peptide Group Meeting. The conference took place the beautiful beachside town of Port Leucate, France and Exploration Science was there. Please tune in to part one of a 3-episode special highlighting the science and scientists at the meeting. Our first interview is with Professor Gilles Subra. Professor Subra discusses his diverse research program including work on peptide synthesis via ball-milling and biocompatible hydrogels.

Katie is a 10-year-old science enthusiast with a keen interest in aromaticity, nucleophilic aromatic substitution reactions, and genetics. Her favorite molecule is nitrobenzene. This young explorer is also fascinated by quantum physics and is debating between a career as an astronaut or a particle physicist. She wants people to know that just because you love science doesn’t mean you can’t have a life outside of studying. She particularly enjoys art, music, sports, and hanging out with friends.

In this episode of Exploration Science, I sat down with the first and only APS American Peptide Idol, Dr. Meritxell Teixido. Dr. Teixido is the founder, CEO, and CSO of Gate2Brain, a barrier breaking company delivering therapeutics across the blood-brain barrier. We discussed the work Gate2Brain is doing in pediatric oncology, dove into the technology, and talked about empathetic leadership and the power of diversity.

In this episode of Exploration Science, Professors Anna Maria Papini and Paolo Rovero talk about their research in peptide science from immunology to developing standards for large-scale production of peptides with Microwave-Assisted SPPS under GMP compliance.

References

An Optimized Safe Process from Bench to Pilot cGMP Production of API Eptifibatide Using a Multigram-Scale Microwave-Assisted Solid-Phase Peptide Synthesizer. Annunziata D’Ercole, Lorenzo Pacini, Giuseppina Sabatino, Matteo Zini, Francesca Nuti, Arianna Ribecai, Alfredo Paio, Paolo Rovero, and Anna Maria Papini. Organic Process Research & Development 2021 25 (12), 2754-2771. DOI: 10.1021/acs.oprd.1c00368

An Optimized Scalable Fully Automated Solid-Phase Microwave-Assisted cGMP-Ready Process for the Preparation of Eptifibatide. Giuseppina Sabatino, Annunziata D’Ercole, Lorenzo Pacini, Matteo Zini, Arianna Ribecai, Alfredo Paio, Paolo Rovero, and Anna Maria Papini. Organic Process Research & Development 2021 25 (3), 552-563. DOI: 10.1021/acs.oprd.0c00490

In this episode of Exploration Science, Professors Anna Maria Papini and Paolo Rovero talk about their research in peptide science from immunology to developing standards for large-scale production of peptides with Microwave-Assisted SPPS under GMP compliance.

References

An Optimized Safe Process from Bench to Pilot cGMP Production of API Eptifibatide Using a Multigram-Scale Microwave-Assisted Solid-Phase Peptide Synthesizer. Annunziata D’Ercole, Lorenzo Pacini, Giuseppina Sabatino, Matteo Zini, Francesca Nuti, Arianna Ribecai, Alfredo Paio, Paolo Rovero, and Anna Maria Papini. Organic Process Research & Development 2021 25 (12), 2754-2771. DOI: 10.1021/acs.oprd.1c00368

An Optimized Scalable Fully Automated Solid-Phase Microwave-Assisted cGMP-Ready Process for the Preparation of Eptifibatide. Giuseppina Sabatino, Annunziata D’Ercole, Lorenzo Pacini, Matteo Zini, Arianna Ribecai, Alfredo Paio, Paolo Rovero, and Anna Maria Papini. Organic Process Research & Development 2021 25 (3), 552-563. DOI: 10.1021/acs.oprd.0c00490

In this episode of exploration science, Professors Danny Chou and Helena Safavi take a deep dive into predatory cone snail insulins. These unique insulins, components of the predator’s fish-disorienting venom, are uncovering opportunities to discover new medicines as well as gain insight into signaling pathways of the human insulin receptor.  

References and Links  

Dr. Danny Chou: https://profiles.stanford.edu/danny-chou 

Dr. Helena Safavi: https://helenasafavi.com/our-group/ 

Safavi-Hemami, H. et al. Specialized insulin is used for chemical warfare by fish-hunting cone snails. PNAS 112 (6) 1743-1748 (2015). https://doi.org/10.1073/pnas.1423857112 

Menting, J. et al. A minimized human insulin-receptor-binding motif revealed in a Conus geographus venom insulin. Nat Struct Mol Biol 23, 916–920 (2016). https://doi.org/10.1038/nsmb.3292 

De Meyts, P. Structural basis for the poisonous activity of a predator's venom insulin. Nat Struct Mol Biol 23, 872–874 (2016). https://doi.org/10.1038/nsmb.3304 

Ahorukomeye, P. et al. Fish-hunting cone snail venoms are a rich source of minimized ligands of the vertebrate insulin receptor. eLife 2019;8:e41574 DOI: 10.7554/eLife.41574  

Jiracek, J. and Zakova, L. From venom peptides to a potential diabetes treatment. eLife 2019;8:e44829.DOI: https://doi.org/10.7554/eLife.44829 

Xiong, X. et al. A structurally minimized yet fully active insulin based on cone-snail venom insulin principles. Nat Struct Mol Biol 27, 615–624 (2020). https://doi.org/10.1038/s41594-020-0430-8

Sophia is a 12-year-old biochemistry student in Dr. Daniel Fried’s class. She called in from Perth, Australia to discuss her excitement around biochemistry, space metals, obstetrics, and neon, because it glows.

In Exploration Science Episode 5, Dr. Ved Srivastava, a former president of the American Peptide Society, past co-chair of the American Peptide Symposium, and current VP of Chemistry at Aktis Oncology, walks us through the process of developing peptide therapeutics from discovery to commercialization. Ved is a peptide expert with over 25 years of experience in peptide therapeutics and is the editor of 5 books focused on peptides. This episode has a special mention of the work by Guangcheng Jiang et al. on Degarelix as well as callouts to the initial development of microwave-assisted peptide synthesis and coming breakthroughs in AI and machine learning by the pioneering work at companies like Peptilogics, Pepticom, and Nuritas.

The views and opinions expressed by my guest, Ved Srivastava, are his and do not necessarily reflect the views and opinions of any organization.

Links and references:

1. Links to recent books focused on peptide therapeutics, https://www.amazon.com/vedsrivastava

2. Peptide Therapeutics: Strategy for Chemistry Manufacturing and Control (CMC) (https://pubs.rsc.org/en/content/ebook/978-1-78801-433-5)

3. Implantable Technologies: Peptides and Small Molecules Drug Delivery (https://pubs.rsc.org/en/content/ebook/978-1-83916-222-0)

4. Peptide-based Drug Discovery: Challenges and New Therapeutics (https://pubs.rsc.org/en/content/ebook/978-1-78262-732-6)

5. Comprehensive Medicinal Chemistry III - Volume 7: Biologics Medicine ([www.elsevier.com]www.elsevier.com)

6. ‘Peptide 2015’ (https://www.americanpeptidesociety.org/assets/pdf-files/proceedings/24.pdf)

7. USP Workshop: https://www.usp.org/events-training/workshops/therapeutic-peptides-and- oligonucleotides

8. Degarelix: DOI: 10.1021/jm0003900

In Exploration Science, Episode 4, we continue our exploration of enzyme-mediated technologies in peptide and protein science. As a follow-up to a question posed in Episode 2, the CEO of EnzyTag, Leendert van den Bos, and Peptide Expert, Rodney Lax, tell us about the growing utility of Chemo-Enzymatic Peptide Synthesis (CEPS) from discovery to manufacturing.

Links and references:

Development of omniligase: https://doi.org/10.1016/j.csbj.2021.02.002

Scale-up work on Exenatide (EnzyPep / PPL collaboration): https://doi.org/10.1039/c9gc03600h

Publication with Danny Chou: https://chemrxiv.org/engage/chemrxiv/article-details/618162db81c4fc61d3ea4954.

Omniligase kit https://enzytag.com/ligation-kit/

CEPS Technology - https://www.youtube.com/watch?v=vtEUWmy-oEM

Protein synthesis - https://www.youtube.com/watch?v=YnMoBs1jbAw

In Episode 3 of Exploration Science, Trishul Shah, Director of Business Development at PolyPeptide Group, walks through the process of personalized medicine from needle to needle. Jon Collins, Vice President of Business Development at CEM, also joins us to discuss some challenges faced by the field of peptide-based personalized medicine and opportunities for technology to help.

Andrea Castro, Maurizio Zanetti, Hannah Carter. Neoantigen Controversies. Annual Review of Biomedical Data Science 2021 4:1, 227-253 https://doi.org/10.1146/annurev-biodatasci-092820-112713

https://www.polypeptide.com/wp-content/uploads/2019/12/NeoAntigen.pdf

https://www.polypeptide.com/neoantigen-peptides-napp/

In this episode of exploration science, I sat down with Dr. Christina Boville and Dr. Andrew Buller. Tina and Andrew were postdocs in the laboratory of Professor Francis Arnold where they studied directed evolution. While they worked on the same project in the Arnold lab, they took very different career paths.

Tina is the CEO and co-founder of Aralez Bio, a biotech company based on the sustainable manufacturing of novel amino acids via biocatalysis. Andrew on the other hand, has pursued an academic career and is currently an assistant professor in the Departments of Chemistry and Biochemistry at the University of Wisconsin-Madison. Andrew’s research is focused on the discovery of biocatalytic reactions to better understand protein engineering.

Tina and Andrew dive into scientific applications of biocatalysis, business challenges and opportunities, the green benefits of biocatalytic approaches, and some tasty chemistry.

Weblinks:

https://ipib.wisc.edu/staff/buller-andrew/

https://aralezbio.com/publications/

References:

Doyon, T.J., Kumar, P., Thein, S., Kim, M., Stitgen, A., Grieger, A.M., Madigan, C., Willoughby, P.H. and Buller, A.R. (2022), Scalable and Selective β-Hydroxy-α-Amino Acid Synthesis Catalyzed by Promiscuous l-Threonine Transaldolase ObiH. ChemBioChem. https://doi.org/10.1002/cbic.202100577

Rix, G., Watkins-Dulaney, E.J., Almhjell, P.J. et al. Scalable continuous evolution for the generation of diverse enzyme variants encompassing promiscuous activities. Nat. Commun. 11, 5644 (2020). https://doi.org/10.1038/s41467-020-19539-6

In this episode of Exploration Science, I sat down with Dr. Fernando Albericio, Dr. Beatriz G. de la Torre, and Jonathan Collins at the 2021 TIDES meeting in Boston to discuss their thoughts on peptide therapeutics, manufacturing, and the greening of peptide science. Fernando and Beatriz are professors at the University of KwaZulu Natal, South Africa. Jon is the VP of Business Development at CEM. 

References: Beatriz G. de la Torre, Shaveer Ramkisson, Fernando Albericio, John Lopez. Refractive Index: The Ultimate Tool for Real-Time Monitoring of Solid-Phase Peptide Synthesis. Greening the Process. Organic Process Research & Development 2021, 25 (4), 1047-1053. DOI: 10.1021/acs.oprd.1c00051 

Srinivasa Rao Manne, Omar Luna, Gerardo A. Acosta, Miriam Royo, Ayman El-Faham, Gyorgy Orosz, Beatriz G. de la Torre, and Fernando Albericio. Amide Formation: Choosing the Safer Carbodiimide in Combination with OxymaPure to Avoid HCN Release. Organic Letters 2021 23 (17), 6900-6904. DOI: 10.1021/acs.orglett.1c02466 

N-Butylpyrrolidinone as Alternative Solvent for Solid-Phase Peptide Synthesis. John Lopez, Stefan Pletscher, Andreas Aemissegger, Christoph Bucher, and Fabrice Gallou. Organic Process Research & Development 2018 22 (4), 494-503. DOI: 10.1021/acs.oprd.7b00389

In this episode of Exploration Science, I sat down with Dr. Fernando Albericio, Dr. Beatriz G. de la Torre, and Jonathan Collins at the 2021 TIDES meeting in Boston to discuss their thoughts on peptide therapeutics, manufacturing, and the greening of peptide science. Fernando and Beatriz are professors at the University of KwaZulu Natal, South Africa. Jon is the VP of Business Development at CEM.

References:

1. Beatriz G. de la Torre, Shaveer Ramkisson, Fernando Albericio, John Lopez. Refractive Index: The Ultimate Tool for Real-Time Monitoring of Solid-Phase Peptide Synthesis. Greening the Process. Organic Process Research & Development 2021, 25 (4), 1047-1053. DOI: 10.1021/acs.oprd.1c00051
2. Srinivasa Rao Manne, Omar Luna, Gerardo A. Acosta, Miriam Royo, Ayman El-Faham, Gyorgy Orosz, Beatriz G. de la Torre, and Fernando Albericio. Amide Formation: Choosing the Safer Carbodiimide in Combination with OxymaPure to Avoid HCN Release. Organic Letters 2021 23 (17), 6900-6904. DOI: 10.1021/acs.orglett.1c02466
3. N-Butylpyrrolidinone as Alternative Solvent for Solid-Phase Peptide Synthesis. John Lopez, Stefan Pletscher, Andreas Aemissegger, Christoph Bucher, and Fabrice Gallou. Organic Process Research & Development 2018 22 (4), 494-503. DOI: 10.1021/acs.oprd.7b00389