Episoder
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Carbohydrate chemistry, the final frontier. These ubiquitous building blocks of life are still the most challenging biomolecules to manipulate due to their structural diversity and complexity. A realm where only the bravest creative chemists can go, to deeply understand their biological importance, explore and embrace their therapeutic value. The use of carbohydrates as actives is an emerging field with a vast potential in several areas like cancer treatment, rare diseases or infections.
Our guest today is László Somsák, Professor of Organic Chemistry at the University of Debrecen, Expert in the synthesis of glycomimetics and biologically active carbohydrates.
László has been working at Debrecen University for exactly 40 years now, with a main research interest in designing novel synthetic routes to create carbohydrates, and discover glycomimetics, glycopeptidomimetics, and lectin inhibitors. He is a board member of nearly all local and international carbohydrate organizations and serves in the editorial board of the prestigious journal, CarboHydrate Research. He has almost 400 publications available on the topic.
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As we already learned in the past weeks, glycoscience is certainly an interdisciplinary subject where both chemistry and biology play a critical role in understanding and success. Steering a ship in these waters is a very complex challenge that needs focus and persistence.
Our guest this week, Barbara Richichi, Associate Professor of Chemistry at the University of Florence is a captain on such a ship and will help us understand how carbohydrates could be used as building blocks of complex nanomaterials and how glycomimetics are designed.
Barbara’s lab (GlycoFluoNano) is engaged in three main areas of Glycoscience that are at the interface between Glycochemistry and Glycobiology, specifically in the: i) synthesis of glycomimetics and glycan-based therapeutics; ii) synthesis and functionalization of glyconanomaterials; and iii) the synthesis of fluorescent probes.
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For decades, scientists lived in a paradigm that cyclodextrins are useful excipients and additives with numerous applications and that’s it. The pioneers came and broke these chains, releasing the true potential of these molecules. First Sugammadex was discovered (which is now a blockbuster drug), and later long known cyclodextrins were re-purposed as active ingredients for various therapeutic indications. Some of these developments are now in phase III and II clinical trials for a rare genetic indication and Alzheimer’s disease.
Research started to flourish both in the academia and industry, and companies like Cyclarity Therapeutics were incorporated focusing on cyclodextrin-based drug discovery and development. Today, our guest is Dr Matthew ‘Oki’ O’Connor, founder and co-CEO of Cyclarity Tx.
Oki is a true longevity warrior, who dedicated all his professional career to this research area. After finishing his studies, Oki almost immediately joined SENS Research Foundation as head of research developing, promoting, and ensuring widespread access to therapies that cure and prevent the diseases and disabilities of aging which he left for Cyclarity eventually. He is also a board member of the Longevity Biotech Fellowship and Senior Reviewer of Vitadao, a decentralized collective funding initiative for early-stage longevity research.
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Over the past weeks, we have talked a lot about Glycoscience and research in this field. But what happens with these compounds and inventions once they fulfill the dream? They get commercialized and manufactured and they start their true journey in the pharmaceutical industry. Roquette Fréres is one of the world’s biggest excipient manufacturers and certainly a leader in sugars and cyclodextrins. Our guest today is Elham Blouet, Global Market Manager for injectables and regional head of biopharma technologies at Roquette.
Elham has a very unique career path that led to her position at Roquette. She has done research work at university, been a responsible pharmacist in a company producing sterile medical devices, has teaching experience with pharmacists assistants and pharmacists, and worked at French Health Competent Authorities, which all led to her way to Roquette, where she also served in different positions.
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In earlier episodes, we have touched the topic of cyclodextrin based drug delivery and even nanotechnology, yet today, with our guest, Erem Bilensoy, we are taking a deep dive. As we will hear today, cyclodextrins are not only capable of solubilizing and stabilizing actives, but in good hands also to remove toxic molecules from the body, enhance cellular delivery, compose targeted drug delivery systems and much more. The possibilities are truly infinite.
Welcome Erem Bilensoy, Professor of Pharmaceutical Technology at Hacettepe University and Owner and CSO at BioGalenica.
Erem’s main research related not only to cyclodextrins but pharmaceutical technology and nanoparticle based drug delivery in general. He has authored close to 100 papers and 15 book chapters. Apart from the academic career, industry has also been present in his life, in 2021 she founded her company BioGalenica and she is the president of the European Federation for Pharmaceutical Sciences EUFEPS. Her current research interests include targeted nanoparticles in cancer therapy, cholesterol-targeted nanoparticles to overcome multidrug drug resistance and enhance cellular delivery, applications of proteomics, metabolomics and lipidomics to develop nanomedicines.
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We already had some interviews with researchers focusing oncyclodextrins, yet no one may understand these compounds' true nature and chemical behavior like our guest today, Matthieu Sollogoub. He is less interested in the traditional uses of cyclodextrins within the pharma industry, like small molecule solubilization and stabilization and focuses much more on creating unique compounds with future and unbelievable applications, truly moonshot goals.
Matthieu is a Professor at Sorbonne Université and President of the Organic Division of the French Chemical Society, yet above all, one of the world’s leading experts in cyclodextrin and carbohydrate medicinal chemistry.
Matthieu is the author of almost 150 scientific publications, several books chapters and patents despite his young age and being one of the most acknowledged key opinion leaders in cyclodextrin chemistry. His background is in chemistry, and he focuses on creating novel cyclodextrins for innovative applications. He has been working as a full professor at Sorbonne for 15 years now and leads maybe the largest carbohydrate (cyclodextrin) chemistry group in Europe.
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Carbohydrates are molecules expressed on the surface of nearly all living cells, and their interaction with carbohydrate-binding proteins is critical to many immunobiological processes. Accordingly, carbohydrates are utilized as antigens in many licensed vaccines against bacterial pathogens. More recently, they have also been considered as adjuvants.
Our Guest today, Luigi Lay, Professor of Chemistry at the University of Milanis specialized in advanced glyco-nanomedicine and carbohydrate-based vaccines and will help us understand how carbohydrates could be used as building blocks, targetors and further components of these complex systems.
Luigi has been working with carbohydrates for a very impressive 30+years, dealing with all major aspects, such as synthesis, analysis, evaluation of biological role, later glycoconjugates leading to nanotechnology and vaccines. He has almost 100 papers in the field and the PI and leader of several international consortia dealing with glycoscience.
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Developing drug delivery systems is a challenging area of the pharmaceutical industry that faces real challenges in the 21st century, like the need for targeted delivery, triggered release, personalized therapy, effective formulation of gene and cell therapy drugs, and the list goes on endlessly. Cyclodextrins, in the classical sense, have limitations in these fields, as they cannot target tissues or release their cargo at will. Unless we apply some tricks to them and chemically modify them so that they can fit such novel applications.
Today, we have with us Professor Francesco Trotta, Professor at the University of Torino, vice-president of the European Cyclodextrin Society, who can tell us more about these challenges as he is a pioneer in advanced drug delivery systems and nanotechnology. Francesco lets us peek into the nanoworld of cyclodextrins with all its possibilities and future prospects.
Professor Trotta’s main research relates not only to cyclodextrins but to pharmaceutical technology in general. He has authored over 100 papers, several key reviews, and books on drug delivery, along with numerous patents. He is a member of over a dozen Italian and international associations including both the European and global cyclodextrin societies.
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Glycoscience is the study of carbohydrates (sugars) and their roles in biology. Today, we are focusing on lectins. Lectins are carbohydrate-binding proteins that are highly specific for sugar groups that are part of other molecules, so cause agglutination of particular cells or precipitation of glycoconjugates andpolysaccharides. Lectins have a role in recognition at the cellular and molecular level and play numerous roles in biological recognition phenomena involving cells, carbohydrates, and proteins. Lectins also mediate attachment and binding of bacteria, viruses, and fungi to their intended targets. Our guest today is Anne Imberty, senior researcher at CNRS Grenoble, whose present research projects are centered on lectins from opportunistic bacteria that are involved in the first steps of infection. Structural characterization of these lectins and of their interaction with human glycoconjugates is opening the route for the design of glycocompounds with anti-bacterial activities.
Anne Imberty has decades of experience in Glycobiology, she worked at different institutions of CNRS (Grenoble, Nantes, Paris) also at University of Toronto. She is the author of over 300 papers, leads diverse fields of research teams in glycoscience, actively participates in education and spreading knowledge.
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Milo Malanga is an author of over 50 scientific publications and several patents despite his young age and one of the most well-connected researchers in this field. His background is in medicinal chemistry, and he focuses on creating novel cyclodextrins for innovative applications. Currently, he is also a principal investigator from CarboHyde in Genegut, a Horizon Europe grant focusing on discovering novel drug delivery systems for oral gene delivery against Crohn’s disease.
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Designing novel sugars and understanding how they work is an extremely challenging task. Accordingly, carbohydrate chemistry and supramolecular carbohydrate chemistry require devotion, persistence and creativity. José Manuel Garcia Fernandez, professor at University of Seville is working on such challenging innovations and discoveries around the uses of novel sugars for innovative applications. José will guide us into the world of cyclodextrin and carbohydrate chemistry, unravel a few mysteries and point out challenges and possibilities of the future from a chemistry point of view.
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Cyclodextrins are cyclic molecules made up of multiple glucose units linked together. They come in three forms: alpha-, beta-, and gamma-cyclodextrin. They are formed by the action of enzymes called cyclodextrin glycosyltransferases from starch. Cyclodextrins have a hydrophobic interior and hydrophilic exterior, which makes them useful for encapsulating hydrophobic molecules in their cavity and this complexation leads to a bunch of potential uses from solubility improvement through stabilization to taste masking or side-effect mitigation. However, developing drug products with cyclodextrins is not always easy and straightforward. And who could tell us more about these challenges than Thorsteinn Loftsson, professor emeritus of pharmaceutical technology from Iceland University, who is a pioneer in this specific area and has several decades of pragmatic experience.
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Glycoscience is the study of carbohydrates (sugars) and their roles in biology. Glycans play critical roles in many biological processes such as cell signaling, cell adhesion, immune response, and protein folding, among others. Glycan analysis and characterization is an increasingly important area for biopharma as understanding glycan profiles helps in the development of new therapeutic agents. It is also important for the creation of biobetters when innovator molecules fall out of patent. Structural analysis of glycans and complex carbohydrates, in particular that of lipopolisaccharides and glycoconjugates is the expertise of our guest today, Anthony Molinaro, Professor of Organic Chemistry at University of Napoli.
