A new route for the preparation of iduronate-2-sulfate glycosides: A new substrate for iduronate-2-sulfatase for screening and diagnosis of Mucopolysaccharidosis-II.

Mucopolysaccharidosis type II (MPS-II) is caused by deficiency of iduronate-2-sulfatase (IDS). Newborn screening and diagnosis of MPS-II is warranted because it allows for earlier treatment leading to a better clinical outcome. Newborn screening of MPS-II is based on measurement of IDS enzymatic activity in dried blood spots using synthetic substrates. Here we describe a new synthetic route for preparation of iduronate-2-sulfate glycosides that allows for completely selective sulfation at the 2-position of the iduronate residue and avoids possible contamination by glucuronate-2-sulfate glycosides, thus avoiding any background interference from glucuronate-2-sulfatase that is also present in dried blood spots. The synthesis also allows for preparation of isotopically labeled IDS product, which is used as an internal standard in tandem mass spectrometry assays of IDS enzymatic activity.