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Article

Membrane-Permeable Octanoyloxybenzyl-Masked cNMPs As Novel Tools for Non-Invasive Cell Assays

1
Organic Chemistry, Department of Chemistry, Faculty of Sciences, University of Hamburg, Martin-Luther-King-Platz 6, D-20146 Hamburg, Germany
2
School of Pharmacy, Medicinal Chemistry Unit, University of Camerino, via S. Agostino 1, 62032 Camerino, Italy
3
University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany
*
Author to whom correspondence should be addressed.
Academic Editor: Christian Ducho
Molecules 2018, 23(11), 2960; https://doi.org/10.3390/molecules23112960
Received: 12 October 2018 / Revised: 6 November 2018 / Accepted: 7 November 2018 / Published: 13 November 2018
(This article belongs to the Special Issue Bioactive Nucleosides and Nucleotides)
Adenine nucleotide (AN) 2nd messengers, such as 3′,5′-cyclic adenosine monophosphate (cAMP), are central elements of intracellular signaling, but many details of their underlying processes remain elusive. Like all nucleotides, cyclic nucleotide monophosphates (cNMPs) are net-negatively charged at physiologic pH which limits their applicability in cell-based settings. Thus, many cellular assays rely on sophisticated techniques like microinjection or electroporation. This setup is not feasible for medium- to high-throughput formats, and the mechanic stress that cells are exposed to raises the probability of interfering artefacts or false-positives. Here, we present a short and flexible chemical route yielding membrane-permeable, bio-reversibly masked cNMPs for which we employed the octanoyloxybenzyl (OB) group. We further show hydrolysis studies on chemical stability and enzymatic activation, and present results of real-time assays, where we used cAMP and Ca2+ live cell imaging to demonstrate high permeability and prompt intracellular conversion of some selected masked cNMPs. Based on these results, our novel OB-masked cNMPs constitute valuable precursor-tools for non-invasive studies on intracellular signaling. View Full-Text
Keywords: cyclic nucleotide monophosphate; bio-reversible protection; acyloxybenzyl phosphate ester cyclic nucleotide monophosphate; bio-reversible protection; acyloxybenzyl phosphate ester
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MDPI and ACS Style

Ruthenbeck, A.; Marangoni, E.; Diercks, B.-P.; Krüger, A.; Froese, A.; Bork, N.I.; Nikolaev, V.O.; Guse, A.H.; Meier, C. Membrane-Permeable Octanoyloxybenzyl-Masked cNMPs As Novel Tools for Non-Invasive Cell Assays. Molecules 2018, 23, 2960. https://doi.org/10.3390/molecules23112960

AMA Style

Ruthenbeck A, Marangoni E, Diercks B-P, Krüger A, Froese A, Bork NI, Nikolaev VO, Guse AH, Meier C. Membrane-Permeable Octanoyloxybenzyl-Masked cNMPs As Novel Tools for Non-Invasive Cell Assays. Molecules. 2018; 23(11):2960. https://doi.org/10.3390/molecules23112960

Chicago/Turabian Style

Ruthenbeck, Alexandra, Elisa Marangoni, Björn-Ph. Diercks, Aileen Krüger, Alexander Froese, Nadja I. Bork, Viacheslav O. Nikolaev, Andreas H. Guse, and Chris Meier. 2018. "Membrane-Permeable Octanoyloxybenzyl-Masked cNMPs As Novel Tools for Non-Invasive Cell Assays" Molecules 23, no. 11: 2960. https://doi.org/10.3390/molecules23112960

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