Preparation of a Cross-Linked Porous Protein Crystal Containing Ru Carbonyl Complexes as a CO-Releasing Extracellular Scaffold

Tabe, Hiroyasu; Fujita, Kazumasa; Abe, Satoshi; Tsujimoto, Masahiko; Kuchimaru, Takahiro; Kizaka‐Kondoh, Shinae; Takano, Mikio; Kitagawa, Susumu; Ueno, Takafumi

doi:10.1021/ic502159x

Cited by 78 publications

(60 citation statements)

References 69 publications

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“…Such effects may originate from HSA-Ru(CO) 2 complexes serving as temporary CO storage molecules. Compatible with this notion, binding of Ru(CO) n fragments, with n ranging from 0 to 3, typically to histidine, has been described (Santos-Silva et al, 2001; Santos et al, 2012; Seixas et al, 2015; Tabe et al, 2015; Valensin et al, 2010). Moreover, Tabe et al (2015) observed CO release from ruthenium carbonyl-incorporated cross-linked hen egg white lysozyme (HEWL).…”

Section: Discussionmentioning

confidence: 98%

“…Compatible with this notion, binding of Ru(CO) n fragments, with n ranging from 0 to 3, typically to histidine, has been described (Santos-Silva et al, 2001; Santos et al, 2012; Seixas et al, 2015; Tabe et al, 2015; Valensin et al, 2010). Moreover, Tabe et al (2015) observed CO release from ruthenium carbonyl-incorporated cross-linked hen egg white lysozyme (HEWL). Loss or release of a carbonyl moiety, however, does not necessarily imply release of CO because CORM-3-mediated adduct formation to HEWL, HSA, and hemoglobin was also shown to result in the release of CO 2 (Santos-Silva et al, 2011).…”

Section: Discussionmentioning

confidence: 98%

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CO-independent modification of K + channels by tricarbonyldichlororuthenium(II) dimer (CORM-2)

Geßner

Sahoo

Swain

et al. 2017

European Journal of Pharmacology

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Although toxic when inhaled in high concentrations, the gas carbon monoxide (CO) is endogenously produced in mammals, and various beneficial effects are reported. For potential medicinal applications and studying the molecular processes underlying the pharmacological action of CO, so-called CO-releasing molecules (CORMs), such as tricabonyldichlororuthenium(II) dimer (CORM-2), have been developed and widely used. Yet, it is not readily discriminated whether an observed effect of a CORM is caused by the released CO gas, the CORM itself, or any of its intermediate or final breakdown products. Focusing on Ca2+- and voltage-dependent K+ channels (KCa1.1) and voltage-gated K+ channels (Kv1.5, Kv11.1) relevant for cardiac safety pharmacology, we demonstrate that, in most cases, the functional impacts of CORM-2 on these channels are not mediated by CO. Instead, when dissolved in aqueous solutions, CORM-2 has the propensity of forming Ru(CO)2 adducts, preferentially to histidine residues, as demonstrated with synthetic peptides using mass-spectrometry analysis. For KCa1.1 channels we show that H365 and H394 in the cytosolic gating ring structure are affected by CORM-2. For Kv11.1 channels (hERG1) the extracellularly accessible histidines H578 and H587 are CORM-2 targets. The strong CO-independent action of CORM-2 on Kv11.1 and Kv1.5 channels can be completely abolished when CORM-2 is applied in the presence of an excess of free histidine or human serum albumin; cysteine and methionine are further potential targets. Off-site effects similar to those reported here for CORM-2 are found for CORM-3, another ruthenium-based CORM, but are diminished when using iron-based CORM-S1 and absent for manganese-based CORM-EDE1.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 98%

CO-independent modification of K + channels by tricarbonyldichlororuthenium(II) dimer (CORM-2)

Geßner

Sahoo

Swain

et al. 2017

European Journal of Pharmacology

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“…These two steps can only be explained as a subsequent binding of two inhibitor molecules to the two different sites on the enzyme. 52 In contrast, to reproduce the curves in the presence of pyrithione (LB) and 2B only one slow irreversible step is needed (k 6 ), since the initial rate is inhibitor independent. A suitable candidate in AKR1C enzymes would be the His53 (PDB code 3NTY) which is on the surface, but only two residues away from the main catalytic Tyr55.…”

Section: The Ruthenium Complexes 1a and 1b Inhibit Akr1c1-akr1c3 Enzymesmentioning

confidence: 99%

Pyrithione-based ruthenium complexes as inhibitors of aldo–keto reductase 1C enzymes and anticancer agents

et al. 2016

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Four ruthenium complexes of clinically used zinc ionophore pyrithione and its oxygen analog 2-hydroxypyridine N-oxide were prepared and evaluated as inhibitors of enzymes of the aldo-keto reductase subfamily 1C (AKR1C). A kinetic study assisted with docking simulations showed a mixed type of inhibition consisting of a fast reversible and a slow irreversible step in the case of both organometallic compounds 1A and 1B. Both compounds also showed a remarkable selectivity towards AKR1C1 and AKR1C3 which are targets for breast cancer drug design. The organoruthenium complex of ligand pyrithione as well as pyrithione itself also displayed toxicity on the hormone-dependent MCF-7 breast cancer cell line with EC50 values in the low micromolar range.

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“…10f ). 76 The CO-releasing reaction was achieved by immobilization of a [cis-Ru(CO) 2 X 4 ] 2− unit at Asp18 in the Ru·CL-HEWL as confirmed by X-ray structural analysis (Fig. 10g).…”

Section: Biomolecular Templatesmentioning

confidence: 78%

“…Ueno and co-workers constructed supramolecular proteins for CORM-2 using the ferritin (Fr) cage, 75 hen-egg white lysozyme (HEWL) crystals, 76 and cypovirus polyhedra crystals (PhCs). 77 The Fr cage, which has an outer diameter of 12 nm, provides accumulation sites for Ru carbonyl moieties in the inner cavity (Fig.…”

Section: Biomolecular Templatesmentioning

confidence: 99%

Design of biomaterials for intracellular delivery of carbon monoxide

2015

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Carbon monoxide (CO) is recognized as one of the most important gas signaling molecules involved in governing various therapeutic responses. Intracellular generation of CO is spatiotemporally controlled by catalytic reactions of heme oxygenases (HOs). Thus, the ability to control intracellular CO delivery with modulation of the CO-release rate in specific amounts and locations is expected to improve our fundamental understanding of the functions of CO and the development of clinical applications. For this purpose, CO-releasing molecules (CORMs) have been developed and investigated in vitro and in vivo. Most CORMs are based on transition metal carbonyl complexes. Recently, various biomaterials consisting of metal carbonyls with biomacromolecular scaffolds have been reported to improve the properties of bare metal carbonyls. In this mini-review, current progress in CO delivery, recent strategies for the development of CORMs, and future directions in this field are discussed.

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Preparation of a Cross-Linked Porous Protein Crystal Containing Ru Carbonyl Complexes as a CO-Releasing Extracellular Scaffold

Cited by 78 publications

References 69 publications

CO-independent modification of K + channels by tricarbonyldichlororuthenium(II) dimer (CORM-2)

CO-independent modification of K + channels by tricarbonyldichlororuthenium(II) dimer (CORM-2)

Pyrithione-based ruthenium complexes as inhibitors of aldo–keto reductase 1C enzymes and anticancer agents

Design of biomaterials for intracellular delivery of carbon monoxide

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