Hyaluronic acid fragmentation

The function of hyaluronic acid was initially confined to the maintenance and sta-bihty of the ECM (96). However, the action of hyaluronic acid varies with its size, which determines its function in a cell-type specific manner (97-101). Hyaluronic acid represents more than 50% of the ECM in the skin. High molecular weight hyaluronic acid (>1,000 kDa) controls tissue water content, ECM lubrication, structural integrity, free oxygen radicals, and distribution of plasma proteins (96,100,101). The synthesis of hyaluronic acid is achieved by hyaluronan synthase-1 to -3 (102,103). The stability of hyaluronic acid varies with its microenvironment, as its half-life is less than 10 min in blood, up to 12 h in the skin, and extends to months in the vitreous gel of the eye (100,101). Hyaluronic acid is the only GAG with a function of its breakdown molecules, as small hyaluronic acid molecules and fragments stimulated the maturation of dentritic cells and the synthesis of proinflammatory IL-lp, IL-12, and TNF-a (103-105). The latter effect seems to be restricted to an interaction of hyaluronic acid fragments with the Toll-like receptor 4 (104,105). The observation that bacterial spreading in the... 

An interesting method of connecting two hyaluronic acid fragments through carboxylic and primary amine functions using the Ugi approach is described in the patent [27]. In the method the primary amine was generated by deacylation, then two molecules were allowed to react in the presence of formaldehyde and cyclohexylisocyanide (Eigure 5.2). The Ugi reaction allowed scientists to make cross-hnked HA with an N-substituted amide bond, in which carboxylic and amino functions came from the different HA molecules. 

Decrease of hyaluronic acid and heparan sulfate proteoglycans Increase of chondroitin sulfate proteoglycans Progressive fragmentation and disappearance of elastic fibers Distortion of sinusoidal architecture and parenchymal damage Cirrhosis End-stage process of liver fibrotic degeneration... 

Fig. 21. In vivo diagnostic application of hyaluronic acid immobilized gold nanoprobes. (A) The fluorescence quenching by nanoparticle surface-energy transfer between Hilyte-647 dye labelled oUgo-HA and gold nanocluster (left) is followed by fluorescence recovery after addition of reactive oxygen species/HAdase which release the dye labeled oUgo-HA fragments. (B) Tail vein injection of GNPs capped with HA conjugates labelled with Hilyte-647 in normal (up) and arthritis (bottom) mice. Adapted from Ref 103. (See Color Plate 43.)...

Fibroblasts-stimulating action Improvement in the coUagen fibers production Derma appears more dense Better quality of elastic fibers that appears longer, sharper, and less fragmented Improvement in the GAG physiological production (hyaluronic acid)... 

FIGURE 5.12 A fragment of hyaluronic acid (geometry was optimized by PM6 method). 

The tetra-, hexa-, and octasaccharide fragments of hyaluronic acid (Scheme 27) [111] have been prepared by repeated glycosylation of a GlcNp(l-4)GlcA acceptor with a disaccharide trichloroacetimidate which was prepared from a trichloroacetyl... 

---