Tracking of fast moving neuronal vesicles with ageladine A

Abstract

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The Alkaloid Ageladine A, Originally Isolated from Marine Sponges, Used for pH-Sensitive Imaging of Transparent Marine Animals

“…As described earlier [11], Ageladine A changes its charge from 0 (pH 9.16) to 1 (pH 5.8) or to 2 (pH 2) (calculated charge distribution), which explains the observed behavior of Ageladine A in living tissues. In sea water, with a pH of about 8.1, Ageladine is mostly uncharged and therefore lipophilic and able to permeate through membranes, thus staining the entire animals.…”

“…In very acidic compartments the dye is highly charged (−2) and the molecule is hardly able to penetrate membranes without active membrane transport processes. As the highly charged molecules are believed to be the most fluorescent molecular microspecies [11], a strong pH-dependent fluorescence in acidic vesicles and acidic tissues can be found. …”

“…We did not assume that pH values could be exactly calculated according to the relation of cells pH i (close to pH 7.4) to acidic pH values in specialized tissues. However, we nevertheless showed pH differences in cells and tissues due to the fluorescence properties of Ageladine A [10,11]. …”

“…Some of its derivates showed increased matrix metalloproteinases inhibition [6,8,9]. The description of the pH-dependent fluorescence of Ageladine A also showed that specific cellular vesicles in nerve cells showed the strongest fluorescence [10,11]. During and after application of 10 µM Ageladine A, there was no evidence for a disturbance of synaptic transmission, which is a very sensitive and vulnerable process indicating a negligible acute toxicity of Ageladine A for cellular and signal transduction processes.…”

Perspectives on the synthesis and use of ageladine A

“…Both lead to 2-(3-oxobutyl)isoindoline-1,3-dione [4]. After bromination of the terminal methyl group 20-22 the phthalimide-protected bromomethyl-ketone [6] is coupled with acetyl-guanidine to form the imidazole ring [7] 23 . The last step to yield 2-acetylaminohistamine is the deprotection of the terminal amino-group.…”