Heparan sulfate proteoglycans consist of a protein core to which one or more heparan sulfate (HS) chains, are covalently linked. Unique saccharide sequences in HS define the specific biological functions of these compounds. Therefore, much interest exists in determining how the assembly of the chains is regulated. After formation of the linkage region, HS chains are polymerized by the addition of alternating N-acetylglucosamine (GlcNAc) and glucuronic acid (GlcA). The chains undergo a series of modification reactions which involve partial N-deacetylation and N-sulfation of GlcNAc units, C5 epimerization of adjacent D-GlcA residues to form iduronic acid (L-IdoA), and O-sulfation at various positions. Most of the enzymes involved in GAG biosynthesis have been purified and cloned from different sources.  A variety of mutants have been isolated from cells in culture. In our studies, we have used a phage display library to select peptides that interact with one of the enzymes involved into GAG biosynthesis. Specific peptides might act as glycosylation inhibitors or probes of enzyme structure. The phage library consists of random 10-mer peptides flanked by two cysteine residues, which form a disulfide bound and cyclize the displayed peptide. The peptides were expressed in the phage capside protein pIII and phage were selected based on binding to recombinant N-deacetylase-N-sulfotransferase from  mouse liver (NDST-1). Five rounds of binding were performed and  clones were selected and sequenced. The results showed that 85% of the selected clones displayed two specific sequences. One of these  presents a repeats motif (BXX), where B is a basic amino acid and X, non charged amino acids. However, the second sequence obtained is formed by non charged amino acids. We are cloning and expressing these selected peptides to obtain chimeras with Glutathione Sulfo-Transferase, in order to check the enzyme activity of NDST-1 in the presence of such peptides. Preliminary results had shown that BXX selected peptide inhibits around 30% NDST-1 enzymatic activity, suggesting that such peptide might bind to HS molecules present at the active site of the enzyme. Supported by FAPESP, CNPq and CAPES