Cleusis associated with the chirality of the isomers as well as with the subtle environment of the complexes (e.g., active ligand and lipophilicity). Therefore, the nucleus is the potential cellular target of chiral Ru complexes for anticancer therapy.Supporting InformationFigure S1 Absorption ML-264 spectra of L-[Ru(phen)2(PHPIP)]2+ (a) and D-[Ru(phen)2(LY2409021 web P-HPIP)]2+ (b). In 10 mM Tris-HCl,100 mM NaCl buffer at 25uC in the presence of increasing amounts of G-quadruplex. [Ru] = 10 mM, [DNA] = 0,0.4 mM from top to bottom. Arrows indicate the change in absorbance upon increasing the DNA concentration. (TIF) Figure S2 CD titration of HTG21 with: a)L-[Ru(phen)2(P-HPIP)]2+, b) D-[Ru(phen)2(P-HPIP)]2+, and c) L/D-[Ru(phen)2(P-HPIP)]2+. In 10 mM Tris buffer, 100 mM NaCl (Ph = 7.4) at 25uC, [HTG21] = 2 mM,[Ru] = 0,8 mM and r = [Ru]/[HTG21].d) Illustration of how chiral ruthenium complexes enantioselectively induce parallel human telomere Gquadruplex to form a mixed G-quadruplex. (TIF) Figure S3 Competition FRET experiment of complexes for the G-quadruplex DNA sequence over duplex DNA. Relative DTm of L-[Ru(phen)2(p-HPIP)]2+ and D-[Ru(phen)2(pHPIP)]2+. r = [ds26]/[F21T]. (TIF)H NMR spectra of complexes dl- Ru(phen)2(p-HPIP)]2+. (TIF)Figure SChiral Ru Complexes Inhibit Telomerase ActivityFigure S5 ESI-MS and absorption spectra of complexes L-[Ru(phen)2(p-HPIP)]2+. (TIF) Figure S6 CD spectra of D-OH and L- OH in MeOH, [Ru] = 50 mM. (TIF) Figure S7 ESI-MS and absorption spectra of complexesTable S1 FRET melting curves for experiments carried out with F21T. DTm values of L-Ru, D- Ru and L/D- Ru at ratio of [Ru]/[G4] = 2, [G4] = 1 mM. (DOC)Author ContributionsConceived and designed the experiments: QQY CW XCY JL. Performed the experiments: QQY DDS. Analyzed the data: QQY CW JL. Contributed reagents/materials/analysis tools: QQY DDS YYL. Wrote the manuscript: QQY. Obtained permission for use of cell line: JL QQY CW.D-[Ru(phen)2(p-HPIP)] . (TIF)2+
The use of positron emission tomography (PET) for visualization of atherosclerosis has been evolving over the last decade. The visualization of the vulnerable plaque using the tracer 18F-FDG is promising [1?], and also 18F-FDG uptake as a surrogate marker for atherosclerotic disease activity shows potential [5,6]. The preclinical in vivo research of 24272870 18F-FDG has mainly focused on rabbits [2,7,8]. As transgenic mouse models have shown their value in atherosclerosis research we have focused on developing the technique of small animal PET for in vivo imaging of atherosclerosis in mice. A study published in 2011 [9] used 18F-FDG for in vivo imaging of mice and their results suggest that the methodcan be used to follow the development of atherosclerosis in murine models. Atherogenesis is a complex disease characterized by inflammation [10,11] and many molecular processes are involved. In this article, we focus on five of these processes represented by different molecular markers: (a) monocyte and macrophage recruitment represented by chemo (C-X-C motif) ligand 1 (CXCL-1), monocyte chemoattractant protein (MCP)-1, and vascular cell adhesion molecule (VCAM)-1, (b) macrophages and inflammation represented by cluster of differentiation molecule (CD)-68 and osteopontin (OPN), (c) scavenger receptors represented by lectinlike oxidized LDL-receptor (LOX)-1, (d) hypoxia represented by hypoxia-inducible factor (HIF)-1a, HIF-2a and vascular endothe-FDG and Gene Expression in Murine Atherosclerosislial growth factor A (VEGF), and (e) th.Cleusis associated with the chirality of the isomers as well as with the subtle environment of the complexes (e.g., active ligand and lipophilicity). Therefore, the nucleus is the potential cellular target of chiral Ru complexes for anticancer therapy.Supporting InformationFigure S1 Absorption spectra of L-[Ru(phen)2(PHPIP)]2+ (a) and D-[Ru(phen)2(P-HPIP)]2+ (b). In 10 mM Tris-HCl,100 mM NaCl buffer at 25uC in the presence of increasing amounts of G-quadruplex. [Ru] = 10 mM, [DNA] = 0,0.4 mM from top to bottom. Arrows indicate the change in absorbance upon increasing the DNA concentration. (TIF) Figure S2 CD titration of HTG21 with: a)L-[Ru(phen)2(P-HPIP)]2+, b) D-[Ru(phen)2(P-HPIP)]2+, and c) L/D-[Ru(phen)2(P-HPIP)]2+. In 10 mM Tris buffer, 100 mM NaCl (Ph = 7.4) at 25uC, [HTG21] = 2 mM,[Ru] = 0,8 mM and r = [Ru]/[HTG21].d) Illustration of how chiral ruthenium complexes enantioselectively induce parallel human telomere Gquadruplex to form a mixed G-quadruplex. (TIF) Figure S3 Competition FRET experiment of complexes for the G-quadruplex DNA sequence over duplex DNA. Relative DTm of L-[Ru(phen)2(p-HPIP)]2+ and D-[Ru(phen)2(pHPIP)]2+. r = [ds26]/[F21T]. (TIF)H NMR spectra of complexes dl- Ru(phen)2(p-HPIP)]2+. (TIF)Figure SChiral Ru Complexes Inhibit Telomerase ActivityFigure S5 ESI-MS and absorption spectra of complexes L-[Ru(phen)2(p-HPIP)]2+. (TIF) Figure S6 CD spectra of D-OH and L- OH in MeOH, [Ru] = 50 mM. (TIF) Figure S7 ESI-MS and absorption spectra of complexesTable S1 FRET melting curves for experiments carried out with F21T. DTm values of L-Ru, D- Ru and L/D- Ru at ratio of [Ru]/[G4] = 2, [G4] = 1 mM. (DOC)Author ContributionsConceived and designed the experiments: QQY CW XCY JL. Performed the experiments: QQY DDS. Analyzed the data: QQY CW JL. Contributed reagents/materials/analysis tools: QQY DDS YYL. Wrote the manuscript: QQY. Obtained permission for use of cell line: JL QQY CW.D-[Ru(phen)2(p-HPIP)] . (TIF)2+
The use of positron emission tomography (PET) for visualization of atherosclerosis has been evolving over the last decade. The visualization of the vulnerable plaque using the tracer 18F-FDG is promising [1?], and also 18F-FDG uptake as a surrogate marker for atherosclerotic disease activity shows potential [5,6]. The preclinical in vivo research of 24272870 18F-FDG has mainly focused on rabbits [2,7,8]. As transgenic mouse models have shown their value in atherosclerosis research we have focused on developing the technique of small animal PET for in vivo imaging of atherosclerosis in mice. A study published in 2011 [9] used 18F-FDG for in vivo imaging of mice and their results suggest that the methodcan be used to follow the development of atherosclerosis in murine models. Atherogenesis is a complex disease characterized by inflammation [10,11] and many molecular processes are involved. In this article, we focus on five of these processes represented by different molecular markers: (a) monocyte and macrophage recruitment represented by chemo (C-X-C motif) ligand 1 (CXCL-1), monocyte chemoattractant protein (MCP)-1, and vascular cell adhesion molecule (VCAM)-1, (b) macrophages and inflammation represented by cluster of differentiation molecule (CD)-68 and osteopontin (OPN), (c) scavenger receptors represented by lectinlike oxidized LDL-receptor (LOX)-1, (d) hypoxia represented by hypoxia-inducible factor (HIF)-1a, HIF-2a and vascular endothe-FDG and Gene Expression in Murine Atherosclerosislial growth factor A (VEGF), and (e) th.
