Synthetic Glycoforms Reveal Carbohydrate-Dependent Bioactivity of Human Saposin D.
Christopher G F GrafChristian SchulzMarina SchmälzleinChristian HeinleinManuel MönnichLukas PerkamsMarkus PüttnerIrene BoosMarkus HessefortJose Nelson Lombana SanchezMichael WeyandClemens SteegbornBernadette BreidenKerstin RossGünter SchwarzmannKonrad SandhoffCarlo UnverzagtPublished in: Angewandte Chemie (International ed. in English) (2017)
The main glycoforms of the hydrophobic lysosomal glycoprotein saposin D (SapD) were synthesized by native chemical ligation. An approach for the challenging solid-phase synthesis of the fragments was developed. Three SapD glycoforms were obtained following a general and robust refolding and purification protocol. A crystal structure of one glycoform confirmed its native structure and disulfide pattern. Functional assays revealed that the lipid-binding properties of three SapD glycoforms are highly affected by the single sugar moiety of SapD showing a dependency of the size and the type of N-glycan.