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Complex polysaccharides, hyaluronic acid or hyaluronan (HA), keratan sulfate (KS), chondroitin sulfates (CSs) and heparin (Hep)/heparan sulfate (HS), are a class of ubiquitous molecules exhibiting a wide range of biological functions. They are widely distributed as glycosaminoglycans (GAGs) sidechains of proteoglycans (PGs) in the extracellular matrix and at cellular level. The recent emergence of improved enzymatic and analytical tools for the study of these complex sugars has produced a virtual explosion in the field of glycomics. In particular, the study of the GAG family of polysaccharides has shed considerable light on the way in which specific carbohydrate structures modulate cellular phenotypes. In addition to the wellknown therapeutic applications of some of these macromolecules, such as HA and derivatives as structure modifying molecules and possessing gel-like properties able to provide functional support for tissues, Hep as an anticoagulant and antithrombotic drug and CS in the treatment of osteoarthritis (OA), this increased understanding of GAG structure-function relationship has led to the discovery of novel pharmaceuticals for the possible treatment of serious diseases, such as cancer. In this paper, the structure and the therapeutic applications of several complex natural polysaccharides, including HA, CS/DS, Hep and their derivatives, are presented and discussed also in the light of the many questions still left unanswered, such as improved preparation and GAG-based drugs with improved properties and new possible therapeutic applications.
Department of Biologia Animale. University of Modena & Reggio Emilia, Italy. Via Campi 213/d, 41100 Modena, Italy.
Publication date: June 1, 2006
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