title: Development of a selective activity-based probe for glycosylated LIPA.
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.
authors.affiliation: Worldwide Medicinal Chemistry, Pfizer Pharmatherapeutics Research and Development, Cambridge, MA 02143, United States. Electronic address: aschwaid@gmail.com.
authors.forename: Adam G
authors.initials: AG
authors.lastname: Schwaid
authors.affiliation: Cardiovascular and Metabolic Diseases Research Unit, Pfizer Pharmatherapeutics Research and Development, Cambridge, MA 02143, United States.
authors.forename: Wanida
authors.initials: W
authors.lastname: Ruangsiriluk
authors.affiliation: Cardiovascular and Metabolic Diseases Research Unit, Pfizer Pharmatherapeutics Research and Development, Cambridge, MA 02143, United States.
authors.forename: Allan R
authors.initials: AR
authors.lastname: Reyes
authors.affiliation: Worldwide Medicinal Chemistry, Pfizer Pharmatherapeutics Research and Development, Groton, CT 06340, United States.
authors.forename: Shawn
authors.initials: S
authors.lastname: Cabral
authors.affiliation: Structural Biology and Biophysics, Center for Chemistry Innovation and Excellence, Pfizer Pharmatherapeutics Research and Development, Groton, CT 06340, United States.
authors.forename: Francis
authors.initials: F
authors.lastname: Rajamohan
authors.affiliation: Worldwide Medicinal Chemistry, Pfizer Pharmatherapeutics Research and Development, Cambridge, MA 02143, United States.
authors.forename: Meihua
authors.initials: M
authors.lastname: Tu
authors.affiliation: Cardiovascular and Metabolic Diseases Research Unit, Pfizer Pharmatherapeutics Research and Development, Cambridge, MA 02143, United States.
authors.forename: Jessica
authors.initials: J
authors.lastname: Ward
authors.affiliation: Worldwide Medicinal Chemistry, Pfizer Pharmatherapeutics Research and Development, Cambridge, MA 02143, United States.
authors.forename: Philip A
authors.initials: PA
authors.lastname: Carpino
mesh_terms: D006031:Glycosylation; D006801:Humans; D062105:Molecular Docking Simulation; D015335:Molecular Probes / Q000032:analysis* / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D015394:Molecular Structure; D002787:Sterol Esterase / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D015335:Molecular Probes; C503451:LIPA protein, human; D002787:Sterol Esterase
keywords: Activity based protein profiling; Glycosylation; LAL; LIPA; Lysosomal acid lipase; Serine hydrolase