Development of a selective activity-based probe for glycosylated LIPA

Bioorg Med Chem Lett. 2016 Apr 15;26(8):1993-6. doi: 10.1016/j.bmcl.2016.02.089. Epub 2016 Mar 2.

Abstract

Loss of LIPA activity leads to diseases such as Wolman's Disease and Cholesterol Ester Storage Disease. While it is possible to measure defects in LIPA protein levels, it is difficult to directly measure LIPA activity in cells. In order to measure LIPA activity directly we developed a LIPA specific activity based probe. LIPA is heavily glycosylated although it is unclear how glycosylation affects LIPA activity or function. Our probe is specific for a glycosylated form of LIPA in cells, although it labels purified LIPA regardless of glycosylation.

Keywords: Activity based protein profiling; Glycosylation; LAL; LIPA; Lysosomal acid lipase; Serine hydrolase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Glycosylation
  • Humans
  • Molecular Docking Simulation
  • Molecular Probes / analysis*
  • Molecular Probes / chemical synthesis
  • Molecular Probes / chemistry
  • Molecular Probes / metabolism*
  • Molecular Structure
  • Sterol Esterase / chemistry*
  • Sterol Esterase / metabolism*

Substances

  • Molecular Probes
  • LIPA protein, human
  • Sterol Esterase