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A protein labeling approach is employed for the localization of a zinc-responsive fluorescent probe in the mitochondria and in the Golgi apparatus of living cells. ZP1, a zinc sensor of the Zinpyr family, was functionalized with a benzylguanine moiety and thus converted into a substrate (ZP1BG) for the human DNA repair enzyme alkylguaninetransferase (AGT or(More)
Trafficking and regulation of mobile zinc pools influence cellular functions and pathological conditions in multiple organs, including brain, pancreas, and prostate. The quest for a dynamic description of zinc distribution and mobilization in live cells fuels the development of increasingly sophisticated probes. Detection systems that respond to zinc(More)
Biological mobile zinc and nitric oxide (NO) are two prominent examples of inorganic compounds involved in numerous signaling pathways in living systems. In the past decade, a synergy of regulation, signaling, and translocation of these two species has emerged in several areas of human physiology, providing additional incentive for developing adequate(More)
Over the last 2 decades, the rapid development of new synthetic routes for the preparation of expanded porphyrin macrocycles has allowed for the exploration of a new frontier consisting of "porphyrin-like" coordination chemistry. In this Account, we summarize our exploratory forays into the still relatively poorly explored area of oligopyrrolic macrocycle(More)
Zinc is a trace element with a multitude of roles in biological systems including structural and cofactor functions for proteins. Although most zinc in the central nervous system (CNS) is protein bound, the CNS contains a pool of mobile zinc housed in synaptic vesicles within a subset of neurons. Such mobile zinc occurs in many brain regions, such as the(More)
Reactions of the Schiff base oligopyrrolic octaazamacrocycle 1 with BF4- salts of divalent zinc and cadmium result in fluoride anion abstraction and the formation of difluoride-bridged metal complexes. X-ray diffraction analyses provide support for the notion that hydrogen-bonding interactions, involving the N-H groups of the macrocycle and the coordinated(More)
Iron scavengers (chelators) offer therapeutic opportunities in anticancer drug design by targeting the increased demand for iron in cancer cells as compared to normal cells. Prochelation approaches are expected to avoid systemic iron depletion as chelators are liberated under specific intracellular conditions. In the strategy described herein, a disulfide(More)
A disulfide bond is incorporated in the scaffold of thiosemicarbazone iron chelators as a reduction/activation switch. Following reduction, thiol-containing ligands stabilize iron ions in their trivalent oxidation state. The antiproliferative activity of the new chelating systems is assessed in human cancer cell lines and in normal tissue.
A growing body of evidence suggests that macrophage polarization dictates the expression of iron-regulated genes. Polarization towards iron sequestration depletes the microenvironment, whereby extracellular pathogen growth is limited and inflammation is fostered. In contrast, iron release contributes to cell proliferation, which is important for tissue(More)