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Open AccessJournal ArticleDOI

A new gadolinium-based MRI zinc sensor.

TLDR
The properties of a novel Gd(3+)-based MRI zinc sensor are reported and it is shown to have a relatively strong binding affinity for Zn(2+) (K(D) = 33.6 nM), similar to the affinity of the Zn (2+) ion with HSA alone.
Abstract
The properties of a novel Gd3+-based MRI zinc sensor are reported. Unlike previously reported Gd3+-based MRI contrast agents, this agent (GdL) differs in that the agent alone binds only weakly with human serum albumin (HSA), while the 1:2 GdL:Zn2+ ternary complex binds strongly to HSA resulting in a substantial, 3-fold increase in water proton relaxivity. The GdL complex is shown to have a relatively strong binding affinity for Zn2+ (KD = 33.6 nM), similar to the affinity of the Zn2+ ion with HSA alone. The agent detects as little as 30 μM Zn2+ in the presence of HSA by MRI in vitro, a value slightly more than the total Zn2+ concentration in blood (∼20 μM). This combination of binding affinity constants and the high relaxivity of the agent when bound to HSA suggests that this new agent may be useful for detection of free Zn2+ ions in vivo without disrupting other important biological processes involving Zn2+.

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Journal ArticleDOI

Lanthanide probes for bioresponsive imaging.

TL;DR: Two classes of lanthanide probes are focused on that are subsets of the larger area of metalloimaging: luminescent and magnetic lanthanides.
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Chemistry of MRI Contrast Agents: Current Challenges and New Frontiers

TL;DR: This comprehensive review describes the state of the art of clinically approved contrast agents, their mechanism of action, and factors influencing their safety and efforts to make safer contrast agents either by increasing relaxivity, increasing resistance to metal ion release, or by moving to gadolinium(III)-free alternatives.
Journal ArticleDOI

Nuts and bolts of chemical exchange saturation transfer MRI

TL;DR: The techniques developed over the last decade are summarized with the different imaging strategies and post‐processing methods discussed from a practical point of view, including the description of their relative merits for the detection of CEST agents.
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Responsive magnetic resonance imaging contrast agents as chemical sensors for metals in biology and medicine

TL;DR: This tutorial review highlights progress in the development of responsive magnetic resonance imaging (MRI) contrast agents for detecting and sensing biologically relevant metal ions.
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Selective detection of the reduced form of glutathione (GSH) over the oxidized (GSSG) form using a combination of glutathione reductase and a Tb(III)-cyclen maleimide based lanthanide luminescent 'switch on' assay.

TL;DR: The synthesis of a novel Tb(III) luminescent probe for the detection of thiols is presented, which was poorly emitting in aqueous pH 7 solution in the absence of a thiol, but upon addition ofThiols such as glutathione (GSH), large enhancements were observed, particularly within the physiological pH range.
References
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Journal ArticleDOI

The Amyloid Hypothesis of Alzheimer's Disease: Progress and Problems on the Road to Therapeutics

TL;DR: It has been more than 10 years since it was first proposed that the neurodegeneration in Alzheimer's disease (AD) may be caused by deposition of amyloid β-peptide in plaques in brain tissue and the rest of the disease process is proposed to result from an imbalance between Aβ production and Aβ clearance.
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Relationship between the inhibition constant (K1) and the concentration of inhibitor which causes 50 per cent inhibition (I50) of an enzymatic reaction.

TL;DR: The analysis described shows K I does not equal I 50 when competitive inhibition kinetics apply; however, K I is equal to I 50 under conditions of either noncompetitive or uncompetitive kinetics.
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The neurobiology of zinc in health and disease

TL;DR: The use of zinc in medicinal skin cream was mentioned in Egyptian papyri from 2000 BC, and the number of biological functions, health implications and pharmacological targets that are emerging for zinc indicate that it might turn out to be 'the calcium of the twenty-first century'.
Journal ArticleDOI

Structural Basis of the Drug-Binding Specificity of Human Serum Albumin.

TL;DR: Crystallographic analysis of 17 different complexes of HSA with a wide variety of drugs and small-molecule toxins reveals the precise architecture of the two primary drug-binding sites on the protein, identifying residues that are key determinants of binding specificity and illuminating the capacity of both pockets for flexible accommodation.
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In vivo visualization of gene expression using magnetic resonance imaging

TL;DR: The results offer the promise of in vivo mapping of gene expression in transgenic animals and validate a general approach for constructing a family of MRI contrast agents that respond to biological activity.
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