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.