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DOI: 10.1055/s-0028-1084503
Polysaccharides and oligosaccharides designing: Development of new families of pharmaceutical drug
Polysaccharides are widely distributed in numerous organisms such as animals, plants, fungi and bacteria. Recent studies have suggested that poly- and oligosaccharides reveal physiological functions and are directly implicated in cellular and subcellular communication in biological responses establishment. Consequently, identification and production of new and original poly- and oligosaccharidic structures by enzymatic and chemical designing constitutes a new innovate field of biotechnological applications in therapeutical and cosmetic area in order to produce bio mimetic of glycosaminoglycan. Our project is based on the possibility to produce in large scale all the targeted designing polysaccharides/oligosaccharides and to validate biological activities on fibroblasts cell cultures. The DNA Array method is used to screen the biological activities of the designing poly- and oligosaccharides and of their resulting oligosaccharides. Human fibroblast cell cultures are incubated with different designing drugs. This analysis showed that about the 44 000 human genes, more than 50 genes have been significantly induced. Among them the genes: MMP1 (collagen metabolism), APOE (Response to reactive oxygen species and cytoskeleton organization and biogenesis), SPON1 (Cell adhesion), PTGS2 (Cell mobility and keratinocyte differentiation and regulation of inflammatory response), SECTM1 (regulation of the immune response), PDGFD (Cell proliferation) and PTGS2 (Cell mobility and keratinocytes differentiation) have shown interesting results in the designing carbohydrates/biological activities relationships. After screening, in vitro tests with cell cultures (fibroblasts, keratinocytes), reconstituted skin or skin explants are made to reveal a potential toxicity of the drugs and the biological mechanisms involved in biological activities such as anti aging, regenerative skin care, anti-stretchmarks skin care, after sun care, anticoagulant, immunomodulation, anti-infective actions, anti-tumorigenicity, anti-inflammatory, anti-HIV, conservation of the vascular integrity and tissue regeneration.