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Glycopharmacy – new ways to new drugs
Carbohydrates as new chemical entities?
- The majority of cell signaling, cell-cell adhesion or parasit-host interactions is due to interactions between carbohydrates from the extracellular system and and receptors from the respective cell surface. Cellular receptors are in many cases itself highly glycosylated polymers on the membrane surface, forming the glycocalix of the cell. A positive carbohydrate-carbohydrate or carbohydrate-protein interaction will lead subsequently to a signal transduction into the cell, initiating various physiological effects.
- Our main goal is the controlled influencing of different physiological effects in target cells by means of exogenous oligo- or polysaccharides and proanthocyanidins (physiological engineering).
Some aspects of our recent works on glycobiology:
- Highly acidic, pectin-like polysaccharides show exhibit high bioadhesive activity against epithelial human tissue, especially against GUT tissue (buccal and colonic mucosa). These bioadhesive polymer layers on the luminal side are bound via Ca+2 to endogenous mucins, forming a gel-like system on the tissue. Tissues with such a artifical mucin on top are shielded effectively against exogenous chemical and physical noxes.
- Some chitosan-like oligomers can stimulate the endogenous mucin synthesis and secretion from human colonic tissue.
- Comb-like polysaccharides exhibit a strong anti-mutagenic activity against nitroaromates.
- Some higly acidic polysaccharides can interact with surface receptors of pathogenic microorganisms (e.g. Helicobacter sp., Campylobacter jejuni, Porphyromonas gingivalis) leading to a strongly decreased ability of the germs to adhere to epithelial tissue. For that reasons we call such compounds "antiadhesive polysaccharides" protecting human tissue from the invasion of pathogenic germs.
- Some special polysaccharides can interact with surface receptors of human epithelial skin cells (Keratinocytes), triggering these cells into different physiological states. We know polysaccharides initiating proliferation cycle, while other carbohydrates have a direct influence on the differentiation process towards barrier cells. Other carbohydrates can activate energy metabolism. The different mechanisms towards such effects receptor-mediated, stimulating the different signal transduction pathways.
Potential Strategies of Development
Tissue with bioadhesive layers
- Protection of tissue (Nutraceuticals, inflammatory bowel diseases)
- Tissue-engineering (bioadhesive polysaccahrid layers on implantates)
Control of host-parasit interaction
- Carbohydrates against pathogenic microorganisms (yeasts, Porphyromonas)
- Blocking of the adhesion of GUT-pathogen bacteria (Helicobacter, Campylobacter)
Control of signal transduction (tissue-signaling)
- Wound-healing, skin regeneration
- Production of stimulators for in vitro cell culuture and biotechnology
- Stimulators for liver cell proliferation
Control of cell adhesion
- Antiinflammatory carbohydrates
- Antimetastatic carbohydrates
Methods in use
- Microbiological and cell culture methods (2 labs)
- Organ culture, in situ preparations
- Real time PCR
- Protein analysis
- Phytochemical methods for preparation of special carbohydrates and polyphenols (3 labs)
- Natural product chemistry
- Glycobiology (Oligo-, Polysaccharides, Glyoproteins): structural aspects and pharmacological activities.
- Ethnopharmacology: New pharmacological activities of traditional herbs.
- Stability of plant-derived secondary products and herbal drug material.
- Analytical development and standardization of herbal drug material.
- Polyphenols: Analytical, structural and functional aspects.