Identification of targets of the HIF-1 inhibitor IDF-11774 using alkyne-conjugated photoaffinity probes = 광친화 화학 프로브를 이용한 IDF-11774의 타겟 확인

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dc.contributor.authorHyun Seung Ban-
dc.contributor.authorP Naik-
dc.contributor.authorH M Kim-
dc.contributor.authorBo Kyung Kim-
dc.contributor.authorH Lee-
dc.contributor.authorInhyub Kim-
dc.contributor.authorH Ahn-
dc.contributor.authorY Jang-
dc.contributor.authorK Jang-
dc.contributor.authorY Eo-
dc.contributor.authorK B Song-
dc.contributor.authorK Lee-
dc.contributor.authorMi Sun Won-
dc.date.accessioned2017-04-19T10:26:00Z-
dc.date.available2017-04-19T10:26:00Z-
dc.date.issued2016-
dc.identifier.issn1043-1802-
dc.identifier.uri10.1021/acs.bioconjchem.6b00305ko
dc.identifier.urihttps://oak.kribb.re.kr/handle/201005/13392-
dc.description.abstractWe developed a hypoxia-inducible factor-1 (HIF-1) inhibitor, IDF-11774, as a clinical candidate for cancer therapy. To understand the mechanism of action of IDF-11774, we attempted to isolate target proteins of IDF-11774 using bioconjugated probes. Multifunctional chemical probes containing sites for click conjugation and photoaffinity labeling were designed and synthesized. After fluorescence and photoaffinity labeling of proteins, two-dimensional electrophoresis (2DE) was performed to isolate specific molecular targets of IDF-11774. Heat shock protein (HSP) 70 was identified as a target protein of IDF-11774. We revealed that IDF-11774 inhibited HSP70 chaperone activity by binding to its allosteric pocket, rather than the ATP-binding site in its nucleotide-binding domain (NBD). Moreover, IDF-11774 reduced the oxygen consumption rate (OCR) and ATP production, thereby increasing intracellular oxygen tension. This result suggests that the inhibition of HSP70 chaperone activity by IDF-11774 suppresses HIF-1α refolding and stimulates HIF-1α degradation. Taken together, these findings indicate that IDF-11774-derived chemical probes successfully identified IDF-11774's target molecule, HSP70, and elucidated the mode of action of IDF-11774 in inhibiting HSP70 chaperone activity and stimulating HIF-1α degradation in cancer cells.-
dc.publisherAmer Chem Soc-
dc.titleIdentification of targets of the HIF-1 inhibitor IDF-11774 using alkyne-conjugated photoaffinity probes = 광친화 화학 프로브를 이용한 IDF-11774의 타겟 확인-
dc.title.alternativeIdentification of targets of the HIF-1 inhibitor IDF-11774 using alkyne-conjugated photoaffinity probes-
dc.typeArticle-
dc.citation.titleBioconjugate Chemistry-
dc.citation.number8-
dc.citation.endPage1920-
dc.citation.startPage1911-
dc.citation.volume27-
dc.contributor.affiliatedAuthorHyun Seung Ban-
dc.contributor.affiliatedAuthorBo Kyung Kim-
dc.contributor.affiliatedAuthorInhyub Kim-
dc.contributor.affiliatedAuthorMi Sun Won-
dc.contributor.alternativeName반현승-
dc.contributor.alternativeNameNaik-
dc.contributor.alternativeName김환묵-
dc.contributor.alternativeName김보경-
dc.contributor.alternativeName이홍섭-
dc.contributor.alternativeName김인협-
dc.contributor.alternativeName안희철-
dc.contributor.alternativeName장예린-
dc.contributor.alternativeName장규식-
dc.contributor.alternativeName어유미-
dc.contributor.alternativeName송경빈-
dc.contributor.alternativeName이경-
dc.contributor.alternativeName원미선-
dc.identifier.bibliographicCitationBioconjugate Chemistry, vol. 27, no. 8, pp. 1911-1920-
dc.identifier.doi10.1021/acs.bioconjchem.6b00305-
dc.description.journalClassY-
Appears in Collections:
Division of Biomedical Research > Biotherapeutics Translational Research Center > 1. Journal Articles
Division of Biomedical Research > Personalized Genomic Medicine Research Center > 1. Journal Articles
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