Manganese displacement from Zinpyr-1 allows zinc detection by fluorescence microscopy and magnetic resonance imaging

You, Youngmin; Tomat, Elisa; Hwang, Kyu Suk; Atanasijević, Tatjana; Nam, Wonwoo; Jasanoff, Alan; Lippard, Stephen J.

doi:10.1039/c0cc00179a

Cited by 71 publications

(50 citation statements)

References 18 publications

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“…ZP1 is a calcium-insensitive turn-on Zn(II) sensor with relatively high background fluorescence (Φ = 0.38 at pH 7.0). 74 ZP1 also coordinates Mn(II) ( K d1 = 550 nM, K d2 = 2.2 μM), 75 and this metal ion quenches ZP1 emission. In prior work, we took advantage of the Ca(II) insensitivity and Mn(II)-induced turn-off of ZP1 to probe the Mn(II) affinities of CP-Ser and the metal-binding site mutants CP-Ser ΔHis 3 Asp, ΔHis 4 , and ΔΔ (Table S1).…”

Section: Resultsmentioning

confidence: 99%

Contributions of the S100A9 C-Terminal Tail to High-Affinity Mn(II) Chelation by the Host-Defense Protein Human Calprotectin

et al. 2013

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Human calprotectin (CP) is an antimicrobial protein that coordinates Mn(II) with high affinity in a Ca(II)-dependent manner at an unusual histidine-rich site (site 2) formed at the S100A8/S100A9 dimer interface. We present a 16-member CP mutant family where mutations in the S100A9 C-terminal tail (residues 96–114) are employed to evaluate the contributions of this region, which houses three histidines and four acidic residues, to Mn(II) coordination at site 2. The results from analytical size-exclusion chromatography, Mn(II) competition titrations, and electron paramagnetic resonance spectroscopy establish that the C-terminal tail is essential for high-affinity Mn(II) coordination by native CP in solution. The studies indicate that His103 and His105 (HXH motif) of the tail complete the Mn(II) coordination sphere in solution, affording an unprecedented biological His6 site. These solution studies are in agreement with a Mn(II)-CP crystal structure reported recently (PNAS 2013, 110, 3841). Remarkably high-affinity Mn(II) binding is retained when either H103 or H105 are mutated to Ala, when the HXH motif is shifted from positions 103–105 to 104–106, and when the human tail is substituted by the C-terminal tail of murine S100A9. Nevertheless, antibacterial activity assays employing human CP mutants reveal that the native disposition of His residues is important for conferring growth inhibition against Escherichia coli and Staphylococcus aureus. Within the S100 family, the S100A8/S100A9 heterooligomer is essential for providing high-affinity Mn(II) binding; the S100A7ox, S100A9(C3S), S100A12, and S100B homodimers do not exhibit such Mn(II)-binding capacity.

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Section: Resultsmentioning

confidence: 99%

Contributions of the S100A9 C-Terminal Tail to High-Affinity Mn(II) Chelation by the Host-Defense Protein Human Calprotectin

et al. 2013

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“…To integrate the advantages of fluorescence and MRI sensing, we have devised dual-function MRI/fluorescence probes that are responsive to mobile zinc in aqueous solutions, including (DPA-C 2 ) 2 -TPPS 3 Mn(III) and ZP1Mn 2 (Scheme 2, Zhang et al , 2007; You et al , 2010). Zinc-binding to the DPA units in (DPA-C 2 ) 2 -TPPS 3 Mn(III) changes the relaxivity of Mn(III)-bound water ligands and influences T1 and T2 relaxation in a manner that depends on pH and ionic strength.…”

Section: A Guide To Fluorescent Zinc Probesmentioning

confidence: 99%

Illuminating Mobile Zinc with Fluorescence

Huang

Lippard

2012

Methods in Enzymology

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With the aid of chemoselective sensors, fluorescence microscopy has emerged as an indispensable tool to visualize the distribution and dynamics of various biologically important molecules in live specimens. Motivated by our interest in understanding the chemistry and biology of mobile zinc underlying its physiological and pathological roles, over the past decade our laboratory has developed an extensive library of zinc fluorescence probes. In this article, we provide essential information about our sensor toolbox in order to assist investigators interested to apply our constructs to study various aspects of mobile zinc biology. We illustrate their use with several examples of imaging both exogenous and endogenous mobile zinc in live cells and tissues using various versions of fluorescence microscopy, including confocal and two-photon microscopy.

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“…In some cases, these agents are stimuli-responsive ‘sensors’ that feature enhanced contrast or emission in response to specific cellular signals 22 . For example, Zn(II) 9,10 , Cu(II) 11,12 , NADH 13 and pH 19,20 -responsive dual-modality MRI/fluorescent agents have been designed. Though these systems have provided useful insights into biochemical processes, they are often limited to in vitro imaging studies; the fluorophores used do not absorb/emit in the NIR, which is necessary for in vivo optical imaging.…”

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confidence: 99%

Redox-responsive branched-bottlebrush polymers for in vivo MRI and fluorescence imaging

et al. 2014

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Stimuli-responsive multimodality imaging agents have broad potential in medical diagnostics. Herein, we report the development of a new class of branched-bottlebrush polymer dual-modality organic radical contrast agents—ORCAFluors—for combined magnetic resonance and near-infrared fluorescence imaging in vivo. These nitroxide radical-based nanostructures have longitudinal and transverse relaxation times that are on par with commonly used heavy-metal-based magnetic resonance imaging (MRI) contrast agents. Furthermore, these materials display a unique compensatory redox response: fluorescence is partially quenched by surrounding nitroxides in the native state; exposure to ascorbate or ascorbate/glutathione leads to nitroxide reduction and a concomitant 2- to 3.5-fold increase in fluorescence emission. This behaviour enables correlation of MRI contrast, fluorescence intensity and spin concentration with tissues known to possess high concentrations of ascorbate in mice. Our in vitro and in vivo results, along with our modular synthetic approach, make ORCAFluors a promising new platform for multimodality molecular imaging.

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Manganese displacement from Zinpyr-1 allows zinc detection by fluorescence microscopy and magnetic resonance imaging

Abstract: A paramagnetic manganese complex of a fluorescein-based probe affords a dual-modality zinc sensor featuring an improved fluorescence dynamic range and an MRI readout.

Cited by 71 publications

References 18 publications

Contributions of the S100A9 C-Terminal Tail to High-Affinity Mn(II) Chelation by the Host-Defense Protein Human Calprotectin

Contributions of the S100A9 C-Terminal Tail to High-Affinity Mn(II) Chelation by the Host-Defense Protein Human Calprotectin

Illuminating Mobile Zinc with Fluorescence

Redox-responsive branched-bottlebrush polymers for in vivo MRI and fluorescence imaging

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