DC Field | Value | Language |
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dc.contributor.author | Hyun Seung Ban | - |
dc.contributor.author | P Naik | - |
dc.contributor.author | H M Kim | - |
dc.contributor.author | Bo Kyung Kim | - |
dc.contributor.author | H Lee | - |
dc.contributor.author | Inhyub Kim | - |
dc.contributor.author | H Ahn | - |
dc.contributor.author | Y Jang | - |
dc.contributor.author | K Jang | - |
dc.contributor.author | Y Eo | - |
dc.contributor.author | K B Song | - |
dc.contributor.author | K Lee | - |
dc.contributor.author | Mi Sun Won | - |
dc.date.accessioned | 2017-04-19T10:26:00Z | - |
dc.date.available | 2017-04-19T10:26:00Z | - |
dc.date.issued | 2016 | - |
dc.identifier.issn | 1043-1802 | - |
dc.identifier.uri | 10.1021/acs.bioconjchem.6b00305 | ko |
dc.identifier.uri | https://oak.kribb.re.kr/handle/201005/13392 | - |
dc.description.abstract | We 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.publisher | Amer Chem Soc | - |
dc.title | Identification of targets of the HIF-1 inhibitor IDF-11774 using alkyne-conjugated photoaffinity probes = 광친화 화학 프로브를 이용한 IDF-11774의 타겟 확인 | - |
dc.title.alternative | Identification of targets of the HIF-1 inhibitor IDF-11774 using alkyne-conjugated photoaffinity probes | - |
dc.type | Article | - |
dc.citation.title | Bioconjugate Chemistry | - |
dc.citation.number | 8 | - |
dc.citation.endPage | 1920 | - |
dc.citation.startPage | 1911 | - |
dc.citation.volume | 27 | - |
dc.contributor.affiliatedAuthor | Hyun Seung Ban | - |
dc.contributor.affiliatedAuthor | Bo Kyung Kim | - |
dc.contributor.affiliatedAuthor | Inhyub Kim | - |
dc.contributor.affiliatedAuthor | Mi Sun Won | - |
dc.contributor.alternativeName | 반현승 | - |
dc.contributor.alternativeName | Naik | - |
dc.contributor.alternativeName | 김환묵 | - |
dc.contributor.alternativeName | 김보경 | - |
dc.contributor.alternativeName | 이홍섭 | - |
dc.contributor.alternativeName | 김인협 | - |
dc.contributor.alternativeName | 안희철 | - |
dc.contributor.alternativeName | 장예린 | - |
dc.contributor.alternativeName | 장규식 | - |
dc.contributor.alternativeName | 어유미 | - |
dc.contributor.alternativeName | 송경빈 | - |
dc.contributor.alternativeName | 이경 | - |
dc.contributor.alternativeName | 원미선 | - |
dc.identifier.bibliographicCitation | Bioconjugate Chemistry, vol. 27, no. 8, pp. 1911-1920 | - |
dc.identifier.doi | 10.1021/acs.bioconjchem.6b00305 | - |
dc.description.journalClass | Y | - |
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