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Ryu, Ja-Hyoung
Supramolecular NanoMaterials Lab (SUN)
Research Interests
  • Supramolecular assembly, synthetic peptide assembly, cancer drug delivery


Dual Binding to Orthosteric and Allosteric Sites Enhances the Anticancer Activity of a TRAP1-Targeting Drug

DC Field Value Language Hu, Sung ko Ferraro, Mariarosaria ko Thomas, Ajesh P. ko Chung, Jeong Min ko Yoon, Nam Gu ko Seol, Ji-Hoon ko Kim, Sangpil ko Kim, Han-Ul ko An, Mi Young ko Ok, Haewon ko Jung, Hyun Suk ko Ryu, Ja-Hyoung ko Colombo, Giorgio ko Kang, Byoung Heon ko 2020-05-08T01:35:17Z - 2020-05-06 ko 2020-03 ko
dc.identifier.citation JOURNAL OF MEDICINAL CHEMISTRY, v.63, no.6, pp.2930 - 2940 ko
dc.identifier.issn 0022-2623 ko
dc.identifier.uri -
dc.description.abstract The molecular chaperone TRAP1 is the mitochondrial paralog of Hsp90 and is overexpressed in many cancer cells. The orthosteric ATP-binding site of TRAP1 has been considered the primary inhibitor binding location, but TRAP1 allosteric modulators have not yet been investigated. Here, we generated and characterized the Hsp90 inhibitor PU-H71, conjugated to the mitochondrial delivery vehicle triphenylphosphonium (TPP) with a C-10 carbon spacer, named SMTIN-C10, to enable dual binding to orthosteric and allosteric sites. In addition to tight binding with the ATP-binding site through the PU-H71 moiety, SMTIN-C10 interacts with the E115 residue in the N-terminal domain through the TPP moiety and subsequently induces structural transition of TRAP1 to a tightly packed closed form. The data indicate the existence of a druggable allosteric site neighboring the orthosteric ATP pocket that can be exploited to develop potent TRAP1 modulators. ko
dc.language 영어 ko
dc.publisher AMER CHEMICAL SOC ko
dc.title Dual Binding to Orthosteric and Allosteric Sites Enhances the Anticancer Activity of a TRAP1-Targeting Drug ko
dc.type ARTICLE ko
dc.identifier.scopusid 2-s2.0-85082542231 ko
dc.identifier.wosid 000526404600013 ko
dc.type.rims ART ko
dc.identifier.doi 10.1021/acs.jmedchem.9b01420 ko
dc.identifier.url ko
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