Details

Autor(en) / Beteiligte

• Ruthenbeck, Alexandra
• Marangoni, Elisa
• Diercks, Björn-Ph
• Krüger, Aileen
• Froese, Alexander
• Bork, Nadja I
• Nikolaev, Viacheslav O
• Guse, Andreas H
• Meier, Chris

Titel

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

Ist Teil von

• Molecules (Basel, Switzerland), 2018-11, Vol.23 (11), p.2960

Ort / Verlag

Switzerland: MDPI AG

Erscheinungsjahr

2018

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• 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 Ca 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.