Glycoconjugates: Synthesis, Functional Studies, and Therapeutic Developments
Great reivew on glycoconjugates, their synthesis and pharmaceutical applications from Scripps Research (Sachin S. Shivatare, PhD, Vidya Shivatare and Chi-Huey Wong)
LSU Health Shreveport and CarboHyde collaborate to develop cyclodextrins for restoring sulfide in various disease conditions
Dr. Chris Kevil’s laboratory at LSU Health Shreveport (LSUHS) has discovered that a clinically approved cyclodextrin-based drug called Sugammadex can act as a hydrogen sulfide donor that restores vasoactive hydrogen. This innovation has already gone through initial in vivo testing with promising results.
To take the next leap in development, LSUHS and CarboHyde will start a multiple-staged collaboration project to assess the effects of various cyclodextrins as potential hydrogen sulfide (H2S) donors in methamphetamine-mediated vascular diseases and for various other cardiovascular diseases. Methamphetamine users face a significantly higher risk for cardiovascular disorders, according to a major study published by the Journal of the American Heart Association earlier this year. The Kevil lab has also recently published that chronic methamphetamine use causes cardiovascular dysfunction due to reduced hydrogen sulfide. This poses an additional threat and possible treatment approach for those who use or have already stopped using meth.
LSU Health Shreveport and the Kevil laboratory will focus on comparing the effects of different cyclodextrin derivatives in blood sulfide levels and test the compounds in vitro and in different animal models. CarboHyde’s expertise will be used to select and customize this project’s best-working cyclodextrin derivatives.
“This is exactly the type of research our minds are formed around. We simply admire innovative ideas and out-of-the-box applications of cyclodextrins and other carbohydrates. We keep looking for opportunities to add our knowledge to drive such studies forward. I am sure our collaboration with LSU Health Shreveport and Dr. Kevil will be mutually rewarding and may open novel insights in the application of cyclodextrins in cardiovascular diseases,” said CarboHyde’s CEO József Tóth about this upcoming collaboration.
“Collaboration with carbohydrate expertise at CarboHyde represents a unique opportunity to develop innovative molecules and modalities to treat methamphetamine and other cardiovascular diseases, said Dr. Chris Kevil.
ABOUT CARBOHYDE
CarboHyde is a private preclinical pharmaceutical start-up company specializing in the development of carbohydrate-based APIs. Our team consists of a small group of seasoned scientists with over 50 years of cumulative experience in the field of carbohydrate chemistry, analysis and pharmaceutical development. The company’s core focus is neurodegenerative diseases, yet we also have other pre-clinical programs in various unmet medical indications. Fully embracing the pharmaceutical development ecosystem, we utilize contract research organizations (CRO) and other companies focusing on CMC and clinical development to make our drug development process efficient. CarboHyde’s management team has extensive experience in medicinal chemistry, marketing, and pharmaceutical development. In addition, CarboHyde is supported by experienced advisers, consultants, and carbohydrate veterans.
ABOUT LSU HEALTH SHREVEPORT LSU Health Shreveport (LSUHS) is one of two health sciences centers of the Louisiana State University (LSU) System and home to one of only 155 medical schools in the nation accredited by the Liaison Committee on Medical Education (LCME). The primary mission of LSUHS is to teach, heal, and discover in order to advance the well-being of the state, region and beyond. LSU Health Shreveport encompasses the School of Medicine, School of Graduate Studies and School of Allied Health Professions, Graduate Medical Education (GME), and a robust research enterprise. More than 1,000 students are enrolled in degree programs at any one time, and nearly 600 residents and fellows are enrolled in LSUHS training programs while treating patients at participating sites (hospitals and clinics) throughout north Louisiana. At the heart of LSU Health Shreveport is a strong faculty that includes a number of nationally and internationally acclaimed physicians and scientists. More than 600 strong, they lead research efforts, educate students, train residents and fellows, and provide primary and specialty care to patients throughout the region. Research is a core aspect of our institution’s mission and values, and LSU Health Shreveport and is committed to fostering collaboration and discovery to advance the knowledge and practice of science and medicine. Faculty, staff and students are actively engaged in research across a variety of biomedical areas that ranges from traditional basic science research in the lab to translational research and testing of new treatment and prevention methods in clinical trials. LSU Health Shreveport is home to six research centers, four of which are designated Centers of Research Excellence by the Louisiana Board of Regents, that concentrate on public healthcare needs of the state and region, including cancer, cardiovascular disease, virology, immunology, neuroscience, and addiction. LSU Health Shreveport has established strong community support and is committed to fostering a culture of diversity and inclusion that promotes mutual respect for all. For more information, visit www.lsuhs.edu
Palleon Pharmaceuticals announces issuance of a U.S. Patent for the use of antibody sialidase conjugates
We are always thrilled to see companies adjancing drugs in the field of glycochemistry, just as Palleon Pharmaceuticals. who recently announced patenting engineered human sialidase enzymes that restore antitumor immunity by degrading immunosuppressive sialoglycans on tumors and across immune cell types
Procedure of predicting type 2 diabetes development through analysis of n-glycans attached to the plasma proteins of a healthy person
It’s worth celebrating this discovery by Genos Ltd – Gordan Lauc, Olga Gornik, Frano Vučković, Ivan Gornik on using predicting type 2 diabetes via N-glycan patterns of plasma proteins. Which inventions make glycochemistry shine and show its importance!
Read the full patent on espacenet
Genetically encoded chemical crosslinking of carbohydrate
Covalent linkages are engineered between proteins and carbohydrates under biocompatible conditions. Genetically encoding the chemical crosslinking of proteins to carbohydrates offers a solution to address the low affinity and weak strength of protein–sugar interactions.
The University of California, San Francisco – Shanshan Li, Nanxi Wang, Bingchen Yu Wei Sun Lei Wang present pure beauty!
Read the full article on nature.com
Jellyfish Polysaccharides for Wound Healing Applications
Jellyfish is considered a new potential resource in the food, pharmaceutical, and biomedical industries. In this study presented by Università di Pisa (Chiara Migone Noemi Scacciati Brunella Grassiri Alessandra Braca Dario Puppi Anna Maria Piras et al), skin polysaccharides with glycosaminoglycan features were extracted, and their use as promoters of wound-healing was evaluated
Inclusion Solves Insolubility —Translational Research Cycle from Bedside to Bench and Bench to Bedside for Drug Development Targeting Niemann-Pick Disease Type C
Tetsumi Irie form Kumamoto University explains the differences in the mechanisms of action for HPBCD and HPGCD in the treatment of Niemann-Pick C.
Full article: https://doi.org/10.1248/yakushi.21-00215
Weekly round-up of other carbohydrate-related articles (2022/42)
I.
A significant advantage of using CDs is that they can contribute to the fast onset, the rapid action of different APIs. This is well highlighted in the patent of Fontana Bio and Catalent Pharma Solutions (Anthony Lando and Leon Grother) describing rapidly disintegrating tablets.
https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2022216769
II.
Evaluation of alpha-CD as intestinal tract function improving agent: an immunopotentiating agent, an antimicrobial agent, a hydrogen generator and/or an antioxidant, each comprising CD together with one or more selected from among a butyric acid bacterium, butyric acid, and acetic acid as active ingredients
Nice patent from Cyclochem (Keiji Terao) and Ace Bio Co.
III.
Polyrotaxanes by Toyoda Gosei Americas / ASM and Denka Company Limited / Tokyo Medical and Dental University. The first one is used to make dielectric sheets made of rubber for sensors and actuators; the other promotes osteolysis and/or lipolysis of mesenchymal stem cells (osteoblast or fat differentiation).
These compounds are fascinating and could be so widely used.
IV.
Getting in a weekend mood? Old but gold: CD (polyrotaxane) covered golfball by Sumitomo Rubber AKO! Go out, play, and enjoy!
#golf #polymer #polymerscience #advancedmaterials
https://patentscope.wipo.int/search/en/detail.jsf?docId=US376038326
V.
It is a little adventure to the nanoworld of Zhengzhou University, which build multi-loaded nanovesicles to encapsulate both hydrophilic and hydrophobic drugs and use them to decrease the formation of foam cells and regulate inflammation.
#nanoparticle #atherosclerosis #drugdelivery
https://www.sciencedirect.com/science/article/abs/pii/S0014305722006000?via%3Dihub
VI.
Smoking will not get you healthy, no matter what you put in your cig. But with CDs, at least you can mask the smell a bit, as this patent from KT&G suggests.
#tobacco #smoking #odormasking
https://patentscope.wipo.int/search/en/detail.jsf?docId=US375618843
The synthesis of hyaluronic acid-related oligosaccharides and elucidation of their antiangiogenic activity
Hyaluronic acid-related oligosaccharides were evaluated as potential antiangiogenic agents by N. D. Zelinsky Institute of Organic Chemistry Russian Academy of Sciences – Nadezhda Ustyuzhanina Nikolay Nifantiev
Link to the full article on ScienceDirect
DOI: https://doi.org/10.1016/j.carres.2022.108701Get rights and content
CarboHyde participates in an innovative EU-funded research project to change the treatment paradigm for Crohn’s Disease patients with new RNA-based therapy
GENEGUT, a research project funded by Horizon Europe, is to develop the first oral RNA-based therapy for ileal Crohn’s Disease (CD) – a chronic inflammatory disease of the intestine. The work is set to start on 1st October 2022 and last for four years. The consortium is made up of nine partners from eight European countries, who are all leading experts in their field. CarboHyde will play a crucial role by kick-starting the project by developing custom-made cyclodextrin derivatives, which will help to deliver their RNA cargo to the small intestine.
Addressing the major medical need of Crohn’s Disease
Crohn’s disease (CD), one of the two major disorders under the umbrella term of IBD (Inflammatory Bowel Disease), is a highly prevalent and high-burden chronic inflammatory condition of the gastrointestinal tract (GIT). With up to 3 million people affected in Europe alone, the chronic disease has an accelerating incidence – leading to health costs of over 5 billion euros per year. Most significantly, however, there is no satisfactory treatment.
Role of CarboHyde
The challenging task of CarboHyde will be synthesizing amphiphilic cyclodextrins, which will be used to formulate nanoparticles containing the RNA cargo. CarboHyde will synthesize a library of amphiphilic cyclodextrins, including ones with different excipients, like polyethylene glycol or lipids. Chemically different variations of these excipients will be studied to select the best-performing ones. Nanoparticle formulations with the best working amphiphilic cyclodextrins will be tested to withstand the intestinal environment in different in vivo and in vitro models.
CarboHyde hired a Ph.D. student, Kristof Felegyi, to help the project progress.
Bringing together a multidisciplinary, European network
The expertise required to achieve this ambitious aim is as diverse as the nine partners from eight European countries that will collaborate in GENEGUT.
The project, coordinated by the School of Pharmacy of University College Cork, brings together the European Federation of Crohn’s & Ulcerative Colitis Associations with renowned researchers, expert clinical scientists, SMEs, and large pharma companies with expertise and patented technologies in global proteomics, nanotechnologies, cyclodextrin synthesis, multicellular models, drug delivery systems and production as well as innovation management, stakeholder involvement, and science communication.
A library of novel biomaterials will be synthesized and used to formulate nanoparticles containing therapeutic RNA (siRNA and mRNA). A quality-by-design approach will be applied to develop the nanoparticles for filling into capsules. The resulting nanoparticles will be assessed for safety and efficacy, including the mechanism of action, in a range of advanced in vitro and in vivo models of intestinal inflammation. The clinician, with expertise in diagnosing and treating CD patients based in UCC, will support and guide the overall project ensuring clinical relevance and providing advice on coherent plans for early clinical trials and regulatory submission, thus enabling rapid availability for patients.
Follow the progress of GENEGUT at www.genegut.eu and on Twitter and LinkedIn @GENEGUT_EU to learn about the project’s steps toward a better cure for Crohn’s Disease.
Network
- University College Cork, Ireland
- Bangor University, United Kingdom
- Instituto de Investigação e Inovação em Saúde da Universidade do Porto, Portugal
- Uppsala Universitet, Sweden
- CarboHyde Zrt, Hungary www.carbohyde.com
- Janssen Pharmaceutica NV, Belgium
- Lonza Capsules & Health Ingredients – Capsugel France SAS
- European Federation of Crohn’s and Ulcerative Colitis Associations, Belgium
- accelopment Schweiz AG, Switzerland
| Facts and Figures Funding Programme: HORIZON-HLTH-2021-TOOL Budget: 5.44 million euro Duration: 01.10.2022 – 30.09.2026 Partners: 9 |