2.8.2.35 down downregulation of D4ST-1 in primary human lung fibroblasts leads to a drastic specific reduction of iduronic acid blocks. No change of epimerase activity is found, indicating that the influence of D4ST-1 on epimerization is not due to an altered expression level of the DS-epimerases. Analysis of the dermatan sulfate chains shows that D4ST-1 is essential for the biosynthesis of the disulfated structure iduronic acid-2-O-sulfate-N-acetylgalactosamine-4-O-sulfate, thus confirmed to be strictly connected with the iduronic acid blocks. Also the biologically important residue hexuronic acid-N-acetylgalactosamine-4,6-O-disulfate considerably decreases after D4ST-1 downregulation 703888