Identification of Malate Dehydrogenase 2 as a Target Protein of the HIF-1 Inhibitor LW6 using Chemical Probes†
Prof. Kyeong Lee
College of Pharmacy, Dongguk University-Seoul, 26 Pildong, Junggu, Seoul 100-715 (Korea)
These authors contributed equally to this work.
Search for more papers by this authorDr. Hyun Seung Ban
Medical Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahak-ro, Yuseong-gu, Daejeon 305-806 (Korea)
These authors contributed equally to this work.
Search for more papers by this authorRavi Naik
College of Pharmacy, Dongguk University-Seoul, 26 Pildong, Junggu, Seoul 100-715 (Korea)
Search for more papers by this authorYe Seul Hong
Medical Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahak-ro, Yuseong-gu, Daejeon 305-806 (Korea)
Search for more papers by this authorSeohyun Son
College of Pharmacy, Dongguk University-Seoul, 26 Pildong, Junggu, Seoul 100-715 (Korea)
Search for more papers by this authorDr. Bo-Kyung Kim
Medical Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahak-ro, Yuseong-gu, Daejeon 305-806 (Korea)
Search for more papers by this authorDr. Yan Xia
College of Pharmacy, Dongguk University-Seoul, 26 Pildong, Junggu, Seoul 100-715 (Korea)
Search for more papers by this authorProf. Kyung Bin Song
Department of Food Science and Technology, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon 305-764 (Korea)
Search for more papers by this authorDr. Hong-Sub Lee
ILDONG Pharmaceutical Co. Ltd. 23-9 Seogwoo-dong, Hwaseong, Kyungi-do 445-811 (Korea)
Search for more papers by this authorCorresponding Author
Dr. Misun Won
Medical Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahak-ro, Yuseong-gu, Daejeon 305-806 (Korea)
Medical Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahak-ro, Yuseong-gu, Daejeon 305-806 (Korea)Search for more papers by this authorProf. Kyeong Lee
College of Pharmacy, Dongguk University-Seoul, 26 Pildong, Junggu, Seoul 100-715 (Korea)
These authors contributed equally to this work.
Search for more papers by this authorDr. Hyun Seung Ban
Medical Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahak-ro, Yuseong-gu, Daejeon 305-806 (Korea)
These authors contributed equally to this work.
Search for more papers by this authorRavi Naik
College of Pharmacy, Dongguk University-Seoul, 26 Pildong, Junggu, Seoul 100-715 (Korea)
Search for more papers by this authorYe Seul Hong
Medical Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahak-ro, Yuseong-gu, Daejeon 305-806 (Korea)
Search for more papers by this authorSeohyun Son
College of Pharmacy, Dongguk University-Seoul, 26 Pildong, Junggu, Seoul 100-715 (Korea)
Search for more papers by this authorDr. Bo-Kyung Kim
Medical Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahak-ro, Yuseong-gu, Daejeon 305-806 (Korea)
Search for more papers by this authorDr. Yan Xia
College of Pharmacy, Dongguk University-Seoul, 26 Pildong, Junggu, Seoul 100-715 (Korea)
Search for more papers by this authorProf. Kyung Bin Song
Department of Food Science and Technology, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon 305-764 (Korea)
Search for more papers by this authorDr. Hong-Sub Lee
ILDONG Pharmaceutical Co. Ltd. 23-9 Seogwoo-dong, Hwaseong, Kyungi-do 445-811 (Korea)
Search for more papers by this authorCorresponding Author
Dr. Misun Won
Medical Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahak-ro, Yuseong-gu, Daejeon 305-806 (Korea)
Medical Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahak-ro, Yuseong-gu, Daejeon 305-806 (Korea)Search for more papers by this authorThis work was supported in part by the KRIBB Initiative Program, NRF-2011-0031690, and NRF-2012M3A9C1053532.
Graphical Abstract
Tracking the target: To identify a protein that binds directly to the HIF-1α inhibitor LW6, a series of new chemical probes were synthesized with a clickable tag and/or a photoactivatable moiety. LW6 was found to be localized to the mitochondria (see picture) and MDH2 was identified as a target protein of LW6. These results indicate that the HIF-1α inhibitory activity of LW6 is a consequence of MDH2 suppression.
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