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Photocages as a new approach to modulate zinc signals Public Deposited

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Zinc is one of the most important trace elements in biological systems. Recent advances confirmed the existence of free (labile) zinc and its dynamic role in cellular responses. Zinc has been increasingly recognized as a signaling molecule. Zinc signaling is caused by alternation in free zinc concentrations. In neurons, zinc is released in synaptic clefts. It mediates cell-to-cell signaling and acts like a neurotransmitter. Zinc is also found to be a second messenger akin to calcium, capable of transducting extracellular stimuli into intracellular signaling events. The development of photocaged zinc complexes is a very important approach to facilitate zinc homeostasis and signaling study. Taken advantage of light, such tools can provide time and spatial control of zinc release. In the previous study we have reported ZinCasts, ZinCleavs and NTAdeCage. Based on these work, here three more photocages are developed and named as DPAdeCage, DAPdeCage and XDAPdeCage. These cages adopt a new carbanion-mediated photodecarboxylation strategy and exhibits a prominent improvement in terms of fast photolysis kinetics and biocompatibility. Moreover, both Zn(DAPdeCage) and Zn(XDAPdeCage) are neutral charged complexes therefore can be delivered in cells without extra modification. This is the first time a caged metal complex is reported to be readily cell membrane permeable. While no zinc photocages have been reported in the neurological studies by far, we expect application of these cages in vivo will provide a new technique for those biologists and physiologists who interest in biological free zinc.

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  • 06/09/2021
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  • English
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  • etd-082516-145633
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  • 2016
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  • 2016-08-25
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