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Multiplex imaging and cellular target identification of kinase inhibitors via an affinity-based proteome profiling approach

หน่วยงาน Nanyang Technological University, Singapore

รายละเอียด

ชื่อเรื่อง : Multiplex imaging and cellular target identification of kinase inhibitors via an affinity-based proteome profiling approach
นักวิจัย : Su, Ying , Pan, Sijun , Li, Zhengqiu , Li, Lin , Wu, Xiaoyuan , Hao, Piliang , Sze, Siu Kwan , Yao, Shao Q.
คำค้น : DRNTU::Science::Biological sciences
หน่วยงาน : Nanyang Technological University, Singapore
ผู้ร่วมงาน : -
ปีพิมพ์ : 2558
อ้างอิง : Su, Y., Pan, S., Li, Z., Li, L., Wu, X., Hao, P., et al. (2015). Multiplex imaging and cellular target identification of kinase inhibitors via an affinity-based proteome profiling approach. Scientific reports, 5. , 2045-2322 , http://hdl.handle.net/10220/25151 , http://dx.doi.org/10.1038/srep07724
ที่มา : -
ความเชี่ยวชาญ : -
ความสัมพันธ์ : Scientific reports
ขอบเขตของเนื้อหา : -
บทคัดย่อ/คำอธิบาย :

MLN8237 is a highly potent and presumably selective inhibitor of Aurora kinase A (AKA) and has shown promising antitumor activities. Like other kinase inhibitors which target the ATP-binding site of kinases, MLN8237 might be expected to have potential cellular off-targets. Herein, we report the first photoaffinity-based, small molecule AKA probe capable of both live-cell imaging of AKA activities and in situ proteome profiling of potential off-targets of MLN8237 (including AKA-associating proteins). By using two mutually compatible, bioorthogonal reactions (copper-catalyzed azide-alkyne cycloaddition chemistry and TCO-tetrazine ligation), we demostrate small molecule-based multiplex bioimaging for simultaneous in situ monitoring of two important cell-cycle regulating kinases (AKA and CDK1). A broad range of proteins, as potential off-targets of MLN8237 and AKA's-interacting partners, is subsequently identified by affinity-based proteome profiling coupled with large-scale LC-MS/MS analysis. From these studies, we discover novel AKA interactions which were further validated by cell-based immunoprecipitation (IP) experiments.

บรรณานุกรม :
Su, Ying , Pan, Sijun , Li, Zhengqiu , Li, Lin , Wu, Xiaoyuan , Hao, Piliang , Sze, Siu Kwan , Yao, Shao Q. . (2558). Multiplex imaging and cellular target identification of kinase inhibitors via an affinity-based proteome profiling approach.
    กรุงเทพมหานคร : Nanyang Technological University, Singapore.
Su, Ying , Pan, Sijun , Li, Zhengqiu , Li, Lin , Wu, Xiaoyuan , Hao, Piliang , Sze, Siu Kwan , Yao, Shao Q. . 2558. "Multiplex imaging and cellular target identification of kinase inhibitors via an affinity-based proteome profiling approach".
    กรุงเทพมหานคร : Nanyang Technological University, Singapore.
Su, Ying , Pan, Sijun , Li, Zhengqiu , Li, Lin , Wu, Xiaoyuan , Hao, Piliang , Sze, Siu Kwan , Yao, Shao Q. . "Multiplex imaging and cellular target identification of kinase inhibitors via an affinity-based proteome profiling approach."
    กรุงเทพมหานคร : Nanyang Technological University, Singapore, 2558. Print.
Su, Ying , Pan, Sijun , Li, Zhengqiu , Li, Lin , Wu, Xiaoyuan , Hao, Piliang , Sze, Siu Kwan , Yao, Shao Q. . Multiplex imaging and cellular target identification of kinase inhibitors via an affinity-based proteome profiling approach. กรุงเทพมหานคร : Nanyang Technological University, Singapore; 2558.