期刊
JOURNAL OF INORGANIC BIOCHEMISTRY
卷 117, 期 -, 页码 285-291出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jinorgbio.2012.06.018
关键词
CORM; Ruthenium complexes; Protein crystallography; CO therapy
资金
- Alfama Lda, REQUIMTE [PEst-C/EQB/LA0006/2011]
- Fundacao para a Ciencia e a Tecnologia (FCT) [PTDC/QUI-BIQ/117799/2010, SFRH/BPD/30142/2006, SFRH/BPD/70163/2010, SFRH/BPD/20655/2004, SFRH/BD/77894/2011]
- National Program for Scientific Re-equipmen [REDE/1517/RMN/2005]
- POCI (FEDER)
- Fundação para a Ciência e a Tecnologia [SFRH/BPD/20655/2004, SFRH/BPD/30142/2006, SFRH/BPD/70163/2010, PTDC/QUI-BIQ/117799/2010, SFRH/BD/77894/2011] Funding Source: FCT
Complexes of the general formula fac-[Ru(CO)(3)L-3](2+), namely CORM-2 and CORM-3, have been successfully used as experimental CO releasing molecules (CO-RMs) but their mechanism of action and delivery of CO remain unclear. The well characterized complex [Ru(CO)(3)Cl-2(1,3-thiazole)] (1) is now studied as a potential model CO-RM of the same family of complexes using LC-MS, FTIR, and UV-vis spectroscopy, together with X-ray crystallography. The chemistry of [Ru(CO)(3)Cl-2(1,3-thiazole)] is very similar to that of CORM-3: it only releases residual amounts of CO to the headspace of a solution in PBS7.4 and produces marginal increase of COHb after long incubation in whole blood. 1 also reacts with lysozyme to form Ru adducts. The crystallographic model of the lysozyme-Ru adducts shows only mono-carbonyl Ru species. [Ru(H2O)(4)(CO)] is found covalently bound to a histidine (His15) and to two aspartates (Asp18 and Asp119) at the protein surface. The CO release silence of both 1 and CORM-3 and their rapid formation of protein-Ru(CO)(x)(H2O)(y) (x = 1,2) adducts, support our hypothesis that fac-[Ru(CO)(3)L-3] CO-RMs deliver CO in vivo through the decay of their adducts with plasma proteins. (C) 2012 Elsevier Inc. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据