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Biological Effects of Heparan Sulfates and Regioselectively Modified Heparin-Heparan Mimetics

Institute for Technical and Macromolecular Chemistry Hemocompatible and Biocompatible Biomaterials RWTH Aachen, Worringer Weg 1, D-52074 Aachen, Germany

The heparan sulfates (HS) are structurally the most complex but information rich biopolymers known. They are composed of polysaccharides containing regioselectively distributed carboxyl, sulfate ester, acetyl, amino, and N-sulfonyl groups with sequence- and domain-like arrangements. HS are found ubiquitously on cell surfaces and in extracellular matrices where they are covalently anchored via restricted protein cores. They modulate numerous development cell processes and the pathology of living organisms. HS concentration is extremely low on endothelial cell surfaces (1 pmol/cm²), therefore, they are difficult to isolate and evaluate. Furthermore, their sequence variability is extremely high and the sequence analysis is in its infancy. HS acts as a low affinity receptor which plays a central role in the reception and modulation of a wide range of effector proteins such as growth factors, morphogens, chemokines, enzymes, protease inhibitors.

Water soluble fragments of HS and heparin (HE) enzymatically released or synthetic sequences, analogs of heparinoids and heparanoids (HH) mimetics regioselectively modified oligo- and polysaccharides with HE/HS like functional groups, and nonsaccharide containing structures can modulate effector proteins and influence some of the development and pathological processes. Modulation effects are described for anticoagulant antiproliferative properties, for reducing platelet and plasma protein adhesion as well as inhibition or activating growth factors by the influence of HH mimetics. The advantage of defined high molecular weight substrates are discussed and compared to the low molecular weight mimetics. The potential of HH mimetics opens new approaches and strategies for therapeutic treatment.

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