Reactions of an organoruthenium anticancer complex with 2-mercaptobenzanilide-a model for the active-site cysteine of protein tyrosine phosphatase 1B
文献类型：期刊论文
| 作者 | Han, Yumiao1,2; Luo, Qun1,2; Hao, Xiang2; Li, Xianchan1,2; Wang, Fuyi1,2; Hu, Wenbing1,2; Wu, Kui1,2; Lu, Shuang1,2; Sadler, Peter J.3 |
| 刊名 | DALTON TRANSACTIONS
 |
| 出版日期 | 2011 |
| 卷号 | 40期号:43页码:11519-11529 |
| ISSN号 | 1477-9226 |
| DOI | 10.1039/c1dt11189b |
| 英文摘要 | The organometallic anticancer complex [(eta(6)-p-cymene)Ru(en)Cl]PF(6) (1, en = ethylenediamine) readily reacts with thiols and forms stable sulfenate/sulfinate adducts which may be important for its biological activity. Protein tyrosine phosphatase 1B (PTP1B), a therapeutic target, contains a catalytic cysteinyl thiol and is involved in the regulation of insulin signaling and the balance of protein tyrosine kinase activity. On oxidation, the catalytic Cys215 can form an unusual sulfenyl-amide intermediate which can subsequently be reduced by glutathione. Here we study reactions of 1 with 2-mercaptobenzanilide, 2, a recognized model for the active site of PTP1B. We have characterized crystallographically compound 2 and its oxidized sulfenyl-amide derivative 2-phenyl-1,2-benzisothiazol-3(2H)-one (4), which shows a close structural similarity to the sulfenyl-amide in oxidized PTP1B. At pH 7.4 and 5.3, 1 reacted with 2, affording a mono-ruthenium thiolato complex [(eta(6)-cym)Ru(en)(S-RS)](+) (7(+), R = (C(6)H(4))CONH(C(6)H(5))) and a triply-S-bridged thiolato complex [((eta(6)-cym)Ru)(2)(mu-S-RS)(3)](+) (8(+)), respectively. Coordination of Ru to the S atom in 7 allows formation of a strong H-bond (2.02 angstrom) between the en-NH and the carbonyl oxygen. To assess the possible effect of ruthenium coordination on the redox regulation of PTP1B, reactions of these thiolato products with H(2)O(2) and/or GSH were then investigated, demonstrating that coordination to Ru largely retards both the oxidation (deactivation) of the thiol in compound 2 by H(2)O(2) and the subsequent reduction (reactivation) of the sulfenyl-amide by GSH, implying that the inhibition of complex 1 on PTP1B (IC(50) of 19 mu M) may be attributed to coordination to its catalytic cysteine. |
| 语种 | 英语 |
| WOS记录号 | WOS:000296204100027 |
| 出版者 | ROYAL SOC CHEMISTRY |
| 源URL | [http://ir.iccas.ac.cn/handle/121111/72747]  |
| 专题 | 中国科学院化学研究所 |
| 通讯作者 | Wang, Fuyi |
| 作者单位 | 1.Chinese Acad Sci, CAS Key Lab Analyt Chem Living Biosyst, Inst Chem, Beijing 100190, Peoples R China 2.Chinese Acad Sci, Beijing Natl Lab Mol Sci, Inst Chem, Beijing 100190, Peoples R China 3.Univ Warwick, Dept Chem, Coventry CV4 7AL, W Midlands, England |
| 推荐引用方式 GB/T 7714 | Han, Yumiao,Luo, Qun,Hao, Xiang,et al. Reactions of an organoruthenium anticancer complex with 2-mercaptobenzanilide-a model for the active-site cysteine of protein tyrosine phosphatase 1B[J]. DALTON TRANSACTIONS,2011,40(43):11519-11529. |
| APA | Han, Yumiao.,Luo, Qun.,Hao, Xiang.,Li, Xianchan.,Wang, Fuyi.,...&Sadler, Peter J..(2011).Reactions of an organoruthenium anticancer complex with 2-mercaptobenzanilide-a model for the active-site cysteine of protein tyrosine phosphatase 1B.DALTON TRANSACTIONS,40(43),11519-11529. |
| MLA | Han, Yumiao,et al."Reactions of an organoruthenium anticancer complex with 2-mercaptobenzanilide-a model for the active-site cysteine of protein tyrosine phosphatase 1B".DALTON TRANSACTIONS 40.43(2011):11519-11529. |
入库方式： OAI收割
来源：化学研究所
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