Schwaid Adam G, Ruangsiriluk Wanida, Reyes Allan R, Cabral Shawn, Rajamohan Francis, Tu Meihua, Ward Jessica, Carpino Philip A
Worldwide Medicinal Chemistry, Pfizer Pharmatherapeutics Research and Development, Cambridge, MA 02143, United States.
Cardiovascular and Metabolic Diseases Research Unit, Pfizer Pharmatherapeutics Research and Development, Cambridge, MA 02143, United States.
Bioorg Med Chem Lett. 2016 Apr 15;26(8):1993-6. doi: 10.1016/j.bmcl.2016.02.089. Epub 2016 Mar 2.
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.
LIPA活性丧失会导致诸如沃尔曼病和胆固醇酯贮积病等疾病。虽然可以测量LIPA蛋白水平的缺陷，但很难直接测量细胞中的LIPA活性。为了直接测量LIPA活性，我们开发了一种基于LIPA比活性的探针。LIPA高度糖基化，尽管尚不清楚糖基化如何影响LIPA活性或功能。我们的探针在细胞中对糖基化形式的LIPA具有特异性，尽管它对纯化的LIPA进行标记，而不考虑其糖基化状态。
