Synthetic Glycoforms Reveal Carbohydrate-Dependent Bioactivity of Human Saposin D

Angew Chem Int Ed Engl. 2017 May 2;56(19):5252-5257. doi: 10.1002/anie.201701362. Epub 2017 Apr 5.

Abstract

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.

Keywords: glycopeptide; glycoprotein; ligation; lipid metabolism; oligosaccharide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carbohydrate Conformation
  • Carbohydrates / chemistry*
  • Glycosylation
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Particle Size
  • Saposins / chemical synthesis*
  • Saposins / chemistry
  • Saposins / metabolism*

Substances

  • Carbohydrates
  • Saposins