Newton Ana S, Deiana Luca, Puleo David E, Cisneros José A, Cutrona Kara J, Schlessinger Joseph, Jorgensen William L
Department of Chemistry, Yale University, New Haven, Connecticut 06520-8107, United States.
Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06520-8066, United States.
ACS Med Chem Lett. 2017 May 17;8(6):614-617. doi: 10.1021/acsmedchemlett.7b00154. eCollection 2017 Jun 8.
A competitive fluorescence polarization (FP) assay is reported for determining binding affinities of probe molecules with the pseudokinase JAK2 JH2 allosteric site. The syntheses of the fluorescent and used in the assay are reported as well as results for 10 compounds, including JNJ7706621, NVP-BSK805, and filgotinib (GLPG0634). X-ray crystal structures of JAK2 JH2 in complex with NVP-BSK805, filgotinib, and diaminopyrimidine elucidate the binding poses.
报道了一种用于测定探针分子与假激酶JAK2 JH2变构位点结合亲和力的竞争性荧光偏振（FP）测定法。还报道了该测定法中使用的荧光团的合成以及10种化合物的结果，包括JNJ7706621、NVP-BSK805和非戈替尼（GLPG0634）。JAK2 JH2与NVP-BSK805、非戈替尼和二氨基嘧啶复合物的X射线晶体结构阐明了结合模式。
