The human parvovirus adeno-associated virus (AAV) infects a broad range of cell types, including human, nonhuman primate, canine, murine, and avian. Although little is known about the initial events of virus infection, AAV is currently being developed as a vector for human gene therapy. Using defined mutant CHO cell lines and standard biochemical assays, we demonstrate that heparan sulfate prot...

All Hedgehog morphogens are released from producing cells, despite being synthesized as N- and C-terminally lipidated molecules, a modification that firmly tethers them to the cell membrane. We have previously shown that proteolytic removal of both lipidated peptides, called shedding, releases bioactive Sonic hedgehog (Shh) morphogens from the surface of transfected Bosc23 cells. Using in vivo ...

Heparan sulfate N-deacetylase/N-sulfotransferase (NDST) catalyzes the deacetylation and sulfation of N-acetyl-D-glucosamine residues of heparan sulfate, a key step in its biosynthesis. Recent crystallographic and mutational studies have identified several potentially catalytic residues of the sulfotransferase domain of this enzyme (, J. Biol. Chem. 274:10673-10676). We have used the x-ray cryst...

Most proteoglycans bear either chondroitin sulfate or heparan sulfate chains linked to serine residues at Ser-Gly attachment sites on the core protein. However, only a fraction of proteins with Ser-Gly sites exhibit glycosaminoglycan chains. A variable proportion of these sites may be glycanated, and an unknown mechanism distinguishes whether these sites are for chondroitin sulfate or heparan s...

BACKGROUND Stromal fibroblasts are important determinants of tumor cell behavior. They act to condition the tumor microenvironment, influence tumor growth, support tumor angiogenesis and affect tumor metastasis. Heparan sulfate proteoglycans, present both on tumor and stromal cells, interact with a large number of ligands including growth factors, their receptors, and structural components of t...

BACKGROUND The astonishing thickness of the endothelial glycocalyx, which rivals that of endothelial cells in the microvasculature, was disclosed in the last 15 years. As already demonstrated, this structure plays a key role in the regulation of inflammation and vascular permeability. METHODS AND RESULTS Two components of the glycocalyx, syndecan-1 and heparan sulfate, were measured in arteri...

Collagen-proteoglycan interactions participate in the regulation of matrix assembly and in cell-matrix interactions. We reported previously that a fragment (Ile824-Pro950) of the collagen alpha1(V) chain, HepV, binds to heparin via a cluster of three major basic residues, Arg912, Arg918, and Arg921, and two additional residues, Lys905 and Arg909 (Delacoux, F., Fichard, A., Cogne, S., Garrone, R...

A dynamic mixture of iron complexes was used as a colorimetric sensor for sulfated glycosaminoglycans. The sensing ensemble was prepared by mixing [FeCl(2)(H(2)O)(4)] with dipicolylamine, the functionalized bipyridyl ligand N-(6-aminohexyl)-4'-methyl-2,2'-bipyridine-4-carboxamide, and the dye Evans Blue. Upon addition of the analytes, characteristic changes in the UV-Vis spectrum of the solutio...

We have previously reported that the heparan sulfate-priming glycoside 2-(6-hydroxynaphthyl)-beta-D-xylopyranoside selectively inhibits growth of transformed or tumor-derived cells. To investigate the specificity of this xyloside various analogs were synthesized and tested in vitro. Selective growth inhibition was dependent on the presence of a free 6-hydroxyl in the aglycon. Because cells defi...

BACKGROUND Interaction with heparan sulfate proteoglycans is supposed to provide chemokines with the capacity to immobilize on cell surface and extracellular matrix for accomplishing both tissue homing and signaling of attracted cells. However, the consequences of the exclusive invalidation of such interaction on the roles played by endogenous chemokines in vivo remain unascertained. METHODS ...