Exploration Science with Dr. Wendy Hartsock and Dr. Diedra Shorty – Details, episodes & analysis

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, 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