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 this episode of Exploration Science, Drs. Ronald Frank (AIMS Scientific Products GmbH) and Christian Behn (CEM) discuss the evolution of SPOT Synthesis to generate peptide libraries. They also correct some misinformation and bring to light the ease and utility of applying SPOT arrays to biological studies.   Watch on YouTube: https://youtu.be/MBJFIygXDRg Correction: The founding of AIMS company was in 1998, not 1989.   See the links and references below for some examples of SPOT applications: AIMS Scientific Products http://www.aims-scientific-products.de/index.php CEM MultiPep: https://cem.com/multipep2 Clemens Schulte, Vladimir Khayenko, Amit Jean Gupta, Hans Michael Maric. Low-cost synthesis of peptide libraries and their use for binding studies via temperature-related intensity change. STAR Protocols. Volume 2, Issue 3, 2021, 100605. https://doi.org/10.1016/j.xpro.2021.100605.  Melder FTI, Lindemann P, Welle A, Trouillet V, Heißler S, Nazaré M, Selbach M. Compound Interaction Screen on a Photoactivatable Cellulose Membrane (CISCM) Identifies Drug Targets. ChemMedChem. 2022 Oct 6;17(19):e202200346. doi: 10.1002/cmdc.202200346. Epub 2022 Sep 20. PMID: 35867055; PMCID: PMC9826412.  Mohammed El-Mowafy, Ursula Bilitewski. Identification of possible Ser/Thr/Tyr phosphorylation sites in the fungal histidine kinase CaNik1p by peptide array technique. Bulletin of Faculty of Pharmacy, Cairo University. Volume 56, Issue 1, 2018, Pages 68-72. https://doi.org/10.1016/j.bfopcu.2018.03.007.  Moreno-Yruela, C., Bæk, M., Vrsanova, AE. et al. Hydroxamic acid-modified peptide microarrays for profiling isozyme-selective interactions and inhibition of histone deacetylases. Nat Commun 12, 62 (2021). https://doi.org/10.1038/s41467-020-20250-9.  Meyer et al., Mutations in Disordered Regions Can Cause Disease by Creating Dileucine Motifs. Cell (2018), https://doi.org/10.1016/j.cell.2018.08.019. Rebollo, A., Fliedel, L., Tuffery, P., PEPscan: A Broad-Spectrum Approach for the Characterization of Protein-Binder Interactions? Biomolecules 2022, 12, 178. https://doi.org/10.3390/ Rosie M. Jarrald, Aw W. Liang Alvin, Andrea E. Rawlings, Masayoshi Tanaka, Mina Okochi, and Sarah S. Staniland. Systematic Screening and Deep Analysis of CoPt Binding Peptides Leads to Enhanced CoPt Nanoparticles Using Designed Peptides. Bioconjugate Chemistry 2020 31 (8), 1981-1994. DOI: 10.1021/acs.bioconjchem.0c00348.

In this episode of Exploration Science Dr. Michael Mina, the Chief Scientific Officer of eMed, discusses immunology and the changing landscape of medicine as technology transforms our options for testing and treatment. https://www.emed.com/?hsLang=en

In this episode of Exploration Science, Professor Jennifer Heemstra discusses the biomolecular diversity of peptide nucleic acids, the challenges of our current scientific reward structure, and the opportunity to grow through failure. Bilingual Peptide Nucleic Acids: Encoding the Languages of Nucleic Acids and Proteins in a Single Self-Assembling Biopolymer: https://pubs.acs.org/doi/10.1021/jacs.9b09146 Mentor First Resources: https://mentorfirst.org/

In this episode of Exploration Science, Drs. Gemma Mudd and Kevin McDonnell of Bicycle Therapeutics discuss the Bicycle peptide platform and dive into some of the properties of bicycles that enable the generation of molecules with high affinity, selectivity, and tunable pharmacology. Links: https://www.bicycletherapeutics.com/ Gold-Mediated Multiple Cysteine Arylation for the Construction of Highly Constrained Bicycle Peptides DOI: 10.1021/acs.bioconjchem.2c00288 Bicyclic Peptides as a New Modality for Imaging and Targeting of Proteins Overexpressed by Tumors DOI: 10.1158/0008-5472.CAN-18-0238 Discovery and Optimization of a Synthetic Class of Nectin-4-Targeted CD137 Agonists for Immuno-oncology DOI: 10.1021/acs.jmedchem.2c00505

In this episode of Exploration Science, Professors César de la Fuente from the University of Pennsylvania and Fabien Plisson from CINVESTAV discuss their pursuit of antimicrobial agents and the utility of AI/ML for peptide discovery. Links: Juan CarlosGuido-Patiñoa and FabienPlisson. Profiling hymenopteran venom toxins: Protein families, structural landscape, biological activities, and pharmacological benefits. Toxicon: 10, 14 (2022), 100119. https://doi.org/10.1016/j.toxcx.2022.100119 https://delafuentelab.seas.upenn.edu/research/

In this episode of Exploration Science, Professor David Craik talks about the discovery of the cyclotides and their potential to transform medicine and agriculture. References and links: Database of Cyclic Proteins https://www.cybase.org.au/ Biosynthesis and insecticidal properties of plant cyclotides: The cyclic knotted proteins from Oldenlandia affinis https://doi.org/10.1073/pnas.191366898) Trends in Cyclotide Research https://doi.org/10.1039/9781788010153-00302) Discovery, structure, function, and applications of cyclotides: circular proteins from plants https://doi.org/10.1093/jxb/erw210) T20K: An Immunomodulatory Cyclotide on Its Way to the Clinic https://doi.org/10.1007/s10989-018-9701-1 Synthesis of Proteins by Native Chemical Ligation https://doi.org/10.1126/science.7973629 Elucidation of the Primary and Three-Dimensional Structure of the Uterotonic Polypeptide Kalata B1 https://doi.org/10.1021/bi00013a002 Plant cyclotides: A unique family of cyclic and knotted proteins that defines the cyclic cystine knot structural motif https://doi.org/10.1006/jmbi.1999.3383 Evaluation of the in Vivo Aphrodisiac Activity of a Cyclotide Extract from Hybanthus enneaspermus https://doi.org/10.1021/acs.jnatprod.0c01045) Anthelmintic activity of cyclotides: In vitro studies with canine and human hookworms https://doi.org/10.1016/j.actatropica.2008.11.003 The Engineering of an Orally Active Conotoxin for the Treatment of Neuropathic Pain https://doi.org/10.1002/anie.201000620) Racemic and Quasi-Racemic X-ray Structures of Cyclic Disulfide-Rich Peptide Drug Scaffolds https://doi.org/10.1002/anie.201406563 Is the Mirror Image a True Reflection? Intrinsic Membrane Chirality Modulates Peptide Binding https://doi.org/10.1021/jacs.9b11194 Cyclotides: From Structure to Function https://doi.org/10.1021/acs.chemrev.9b00402) Discovery of Cyclotides from Australasian Plants https://doi.org/10.1071/CH19658)

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.

In episode 3 of Exploration Science, Professor Ingrid Dijkgraaf and Dr. Amine Jmel discuss the potential of tick salivary proteins as lead molecules to develop therapeutics, vaccines, and imaging agents for applications ranging from cardiac disease to livestock immunization. DOI Links: Inhibition of platelet adhesion, thrombus formation, and fibrin formation by a potent αIIbβ3 integrin inhibitor from ticks:  10.1002/rth2.12466 Immunomodulatory Proteins in Tick Saliva from a Structural Perspective: 10.3389/fcimb.2021.769574 Exogenous Integrin αIIbβ3 Inhibitors Revisited: Past, Present and Future Applications: 10.3390/ijms22073366 Structural characterization of anti-CCL5 activity of the tick salivary protein evasin-4: 10.1074/jbc.RA120.013891 Tick Saliva Protein Evasin-3 Allows for Visualization of Inflammation in Arteries through Interactions with CXC-Type Chemokines Deposited on Activated Endothelium: 10.1021/acs.bioconjchem.0c00095 Tick saliva protein Evasin-3 modulates chemotaxis by disrupting CXCL8 interactions with glycosaminoglycans and CXCR2: 10.1074/jbc.RA119.008902 Watch on YouTube: https://youtu.be/EZBAt7Sw-e4

In this episode of Exploration Science, Prof. Adam Duerfeldt and Dr. Henry Shin discuss the science behind their company, Excitant Therapeutics. We learn about their journey into entrepreneurship based on academic research centered around targeting diabetic retinopathy through the activation of PPAR-α (peroxisome proliferator-activated receptor alpha). Dr. Duerfeldt also dives into some of his work in deciphering molecular penetration of Gram-negative bacteria, overstimulation of bacteria to treat infections, and the interrogation of acyldepsipeptides. References and Links https://www.excithera.com/home https://www.oklahoman.com/story/business/information-technology/2019/11/17/falling-in-love-with-eye-research/60420471007/ https://www.velocityokc.com/blog/economy/okc-biotech-front-and-center-as-bio-2022-approaches/ https://www.duerfeldtlabs.com/

Since 2018, @Bachem has been actively developing and expanding its oligonucleotide capabilities. Dr. Daniel Samson VP, Head Oligonucleotides at Bachem discusses future and emerging priorities within industry such as capacity, scalability, cost-effectiveness, lead-time to market, sustainability and the trend towards increased complexity of oligonucleotide-based drugs. Oligonucleotide NCEs (bachem.com) White papers (bachem.com) Innovation transforming oligonucleotide manufacturing (bachem.com)

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 3 of Exploration Science From the Road, we get meeting highlights from two attendees of the joint French Group of Peptides and Proteins meeting and the Belgian Peptide Group meeting in Port Leucate, France. My guests are Dr. Christian Bhen from CEM Germany and Magdalena Verzbeetsska Wierzbicka, a graduate student from the University of Wroclaw. Correction – Degarelix is a 10-residue peptide: https://pubchem.ncbi.nlm.nih.gov/compound/Degarelix#section=Biologic-Description Muttenthaler M, King GF, Adams DJ, Alewood PF. Trends in peptide drug discovery. Nat Rev Drug Discov. 2021 Apr;20(4):309-325. doi: 10.1038/s41573-020-00135-8 Braga Emidio N, Hoffmann W, Brierley SM, Muttenthaler M. Trefoil Factor Family: Unresolved Questions and Clinical Perspectives. Trends Biochem Sci. 2019 May;44(5):387-390. doi: 10.1016/j.tibs.2019.01.004 Antonina A. Berkut et al. Structural Similarity between Defense Peptide from Wheat and Scorpion Neurotoxin Permits Rational Functional Design. JBC 289, Issue 20, 16 May 2014, Pages 14331-14340. https://doi.org/10.1074/jbc.M113.530477 Rajeshwer Vanjari, Deepanjan Panda, Shaswati Mandal, Ganga B. Vamisetti, and Ashraf Brik. Gold(I)-Mediated Rapid Cyclization of Propargylated Peptides via Imine Formation. Journal of the American Chemical Society 2022 144 (11), 4966-4976. DOI: 10.1021/jacs.1c12906 Cheng, Z, Kuru, E, Sachdeva, A & Vendrell Escobar, M. Fluorescent amino acids as versatile building blocks for chemical biology, Nature Reviews Chemistry. 2020. https://www.research.ed.ac.uk/en/publications/fluorescent-amino-acids-as-versatile-building-blocks-for-chemical Geudens, N.; Kovács, B.; Sinnaeve, D.; Oni, F.E.; Höfte, M.; Martins, J.C. Conformation and Dynamics of the Cyclic Lipopeptide Viscosinamide at the Water-Lipid Interface. Molecules 2019, 24, 2257. https://doi.org/10.3390/molecules24122257 EnzyTag https://youtu.be/T-o-X_IHshw https://anchor.fm/exploration-science/episodes/Chemo-Enzymatic-Peptide-Synthesis-e1dnbf5/a-a7atgpf

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

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 Episode 10 of Exploration Science, Drs. Cameron Pye and Joshua Schwochert, co-founders of Unnatural Products, talk about the power of macrocycles to engage formerly undruggable targets to treat human disease. They also walk through the process of starting a company while completing their PhDs and discuss some of the challenges and surprises in the discovery of therapeutics that bridge the gap between large biologics and small molecules. https://www.unnaturalproducts.com/ Kelly CN et.al.  Geometrically Diverse Lariat Peptide Scaffolds Reveal an Untapped Chemical Space of High Membrane Permeability. JACS 2021 143 (2), 705-714 DOI: 10.1021/jacs.0c06115 Furukawa, A et. al. Drug-Like Properties in Macrocycles above MW 1000: Backbone Rigidity versus Side-Chain Lipophilicity.  Angew. Chem. Int. Ed. 2020, 59, 21571-21577. https://doi.org/10.1002/anie.202004550 Naylor MR et al Lipophilic Permeability Efficiency Reconciles the Opposing Roles of Lipophilicity in Membrane Permeability and Aqueous Solubility. 2018 J Med Chem. 2018 61 (24), 11169-11182 DOI: 10.1021/acs.jmedchem.8b01259 Tucker TJ et. al.  A Series of Novel, Highly Potent, and Orally Bioavailable Next-Generation Tricyclic Peptide PCSK9 Inhibitors. J Med Chem. 2021 25;64(22):16770-16800. doi: 10.1021/acs.jmedchem.1c01599

In Exploration Science, episode 9, Dr. Daniel Fried discusses his efforts to bring college-level science education to kids. Akshay, Carolyn, Dylan, Hanson, John, Katie, Rose, Sophia, and Stavro talk about their experience in Dr. Fried’s Biochemstry Literacy for Kids lecture series and dive into some of their favorite science topics. Links: https://biochemistryliteracyforkids.com/ https://twitter.com/DanielFried2 www.youtube.com/channel/UCJx2v6EpmDAjoRdrjgzMIHQ/videos https://www.facebook.com/biochemistry.literacy.for.kids/videos/ https://www.instagram.com/daniel.bennett.fried/

In Episode 8 of Exploration Science, Dr. Ewa Lis, co-founder and CEO of Koliber Biosciences, and Professor Yu-Shan Lin, an associate professor of chemistry at Tufts University, discuss the reality, capability, and potential of artificial intelligence and machine learning. We learn about how they achieved their current positions and tackle some of the misconceptions around AI and ML. Links and References: http://koliberbio.com/ https://ase.tufts.edu/chemistry/lin/paperYSL.html https://www.coursera.org/learn/machine-learning

In Episode 8 of Exploration Science, Dr. Ewa Lis, co-founder and CEO of Koliber Biosciences, and Professor Yu-Shan Lin, an associate professor of chemistry at Tufts University, discuss reality and capability and potential of artificial intelligence and machine learning. In addition, we learned about how they achieved their current positions and tackled some misconceptions around AI and ML. Links and References: http://koliberbio.com/ https://ase.tufts.edu/chemistry/lin/paperYSL.html https://www.coursera.org/learn/machine-learning

In Exploration Science Episode 7, two of the co-founders of Belyntic, Dominik Sarma and Oliver Reimann, discuss PEC technology. Listen in to learn about an alternative to the chromatographic status quo and how a college study group transformed into a groundbreaking technology company. Links and references: Animation Video: https://www.youtube.com/watch?v=W_GA_qp8Y2I Workshop with a general Introduction, and deep dive into Parallel Peptide Purification and Late-Stage Peptide Modification: https://www.youtube.com/watch?v=gtMoxsAfbjg Startup-Story (with Bachem): https://www.youtube.com/watch?v=jOnONSuCtRA Introduction to the new PEC-Linker RC+ (with Bachem): https://www.youtube.com/watch?v=5Q6WvKdDASw PEC for Peptide Modification (with Bachem): https://youtu.be/mJWs113nepk Papers can be found here: https://belyntic.com/publications R. Zitterbart, N. Berger, O. Reimann, G. Noble, S. Lüdtke, D. Sarma, O. Seitz, Traceless parallel peptide purification by a first-in-class reductively cleavable linker system featuring a safety-release, Chemical Science, 2021 https://www.chemistryworld.com/news/hplc-alternative-purifies-peptide-cocktails-in-record-time/4013253.article Blogs: https://belyntic.com/news https://belyntic.com/news-details?title=belyntic-flashback-2021 https://belyntic.com/news-details?title=orthogonal-peptide-purification

In Exploration Science Episode 7, two of the co-founders of Belyntic, Dominik Sarma and Oliver Reimann, discuss PEC technology. Listen in to learn about an alternative to the chromatographic status quo and how a college study group transformed into a groundbreaking technology company. Links and references: Animation Video: https://www.youtube.com/watch?v=W_GA_qp8Y2I Workshop with a general Introduction, and deep dive into Parallel Peptide Purification and Late-Stage Peptide Modification: https://www.youtube.com/watch?v=gtMoxsAfbjg Startup-Story (with Bachem): https://www.youtube.com/watch?v=jOnONSuCtRA Introduction to the new PEC-Linker RC+ (with Bachem): https://www.youtube.com/watch?v=5Q6WvKdDASw PEC for Peptide Modification (with Bachem): https://youtu.be/mJWs113nepk Papers can be found here: https://belyntic.com/publications R. Zitterbart, N. Berger, O. Reimann, G. Noble, S. Lüdtke, D. Sarma, O. Seitz, Traceless parallel peptide purification by a first-in-class reductively cleavable linker system featuring a safety-release, Chemical Science, 2021 https://www.chemistryworld.com/news/hplc-alternative-purifies-peptide-cocktails-in-record-time/4013253.article Blogs: https://belyntic.com/news https://belyntic.com/news-details?title=belyntic-flashback-2021 https://belyntic.com/news-details?title=orthogonal-peptide-purification

In Exploration Science, Episode 6, Part 2, we continue our discussion with Dr. Jan Pawlas of Polypeptide Group and Jonathan Collins of CEM as they dive into some of the intricacies of greening peptide science. The views and opinions expressed by my guest, Jan Pawlas, are his and do not necessarily reflect the views and opinions of PolyPeptide Group. Links and references: A Systems-Based Approach to Green Chemistry: https://doi.org/10.1016/j.isci.2021.103489 Green metrics in Pharmaceutical Development: https://www.sciencedirect.com/science/article/pii/S2452223621001206 Green Chemistry: A Framework for a Sustainable Future: https://pubs.acs.org/doi/full/10.1021/acs.oprd.1c00216 Chemistry 2030: A Roadmap for a New Decade: https://onlinelibrary.wiley.com/doi/10.1002/anie.202014779 Cognitive and Human Factors in Expert Decision Making:Six Fallacies and the Eight Sources of Bias: https://pubs.acs.org/doi/10.1021/acs.analchem.0c00704 The Role of Chemistry and Scientists: https://www.chemistryviews.org/details/ezine/11326355/The_Role_of_Chemistry_and_Scientists.html What Is Discoverable and Why We Need Diversity in Science: https://chemrxiv.org/engage/chemrxiv/article-details/60c74c27f96a00338b28772a Chemophobia cured by chemists: chemists as children of the Sun: https://link.springer.com/article/10.1007%2Fs00706-021-02814-7

In Exploration Science, Episode 6, Part 1, Dr. Jan Pawlas of Polypeptide Group and Jonathan Collins of CEM discuss the intricacies of greening peptide science. We dive into what it really means to be green and talk about some of the opportunities and challenges in greening Fmoc-based SPPS. The views and opinions expressed by my guest, Jan Pawlas, are his and do not necessarily reflect the views and opinions of PolyPeptide Group. Links and references: A Systems-Based Approach to Green Chemistry: https://doi.org/10.1016/j.isci.2021.103489 Green metrics in Pharmaceutical Development: https://www.sciencedirect.com/science/article/pii/S2452223621001206 Green Chemistry: A Framework for a Sustainable Future: https://pubs.acs.org/doi/full/10.1021/acs.oprd.1c00216 Chemistry 2030: A Roadmap for a New Decade: https://onlinelibrary.wiley.com/doi/10.1002/anie.202014779 Cognitive and Human Factors in Expert Decision Making:Six Fallacies and the Eight Sources of Bias: https://pubs.acs.org/doi/10.1021/acs.analchem.0c00704 The Role of Chemistry and Scientists: https://www.chemistryviews.org/details/ezine/11326355/The_Role_of_Chemistry_and_Scientists.html What Is Discoverable and Why We Need Diversity in Science: https://chemrxiv.org/engage/chemrxiv/article-details/60c74c27f96a00338b28772a Chemophobia cured by chemists: chemists as children of the Sun: https://link.springer.com/article/10.1007%2Fs00706-021-02814-7

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 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 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 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