TY  - JOUR
AU  - Reinicke, Justin
AU  - Kitatani, Ryuju
AU  - Masoud, Shadi Sedghi
AU  - Galbraith, Kelly Kawabata
AU  - Yoshida, Wesley
AU  - Igarashi, Ayako
AU  - Nagasawa, Kazuo
AU  - Berger, Gideon
AU  - Yanagihara, Angel
AU  - Nagai, Hiroshi
AU  - Horgen, F. David
TI  - Isolation, Structure Determination, and Synthesis of Cyclic Tetraglutamic Acids from Box Jellyfish Species Alatina alata and Chironex yamaguchii
JO  - Molecules
VL  - 25
IS  - 4
SN  - 1420-3049
CY  - Basel
PB  - MDPI7969
M1  - DZNE-2020-01101
SP  - 883
PY  - 2020
AB  - Cubozoan nematocyst venoms contain known cytolytic and hemolytic proteins, but small molecule components have not been previously reported from cubozoan venom. We screened nematocyst extracts of Alatina alata and Chironex yamaguchii by LC-MS for the presence of small molecule metabolites. Three isomeric compounds, cnidarins 4A (1), 4B (2), and 4C (3), were isolated from venom extracts and characterized by NMR and MS, which revealed their planar structure as cyclic γ-linked tetraglutamic acids. The full configurational assignments were established by syntheses of all six possible stereoisomers, comparison of spectral data and optical rotations, and stereochemical analysis of derivatized degradation products. Compounds 1–3 were subsequently detected by LC-MS in tissues of eight other cnidarian species. The most abundant of these compounds, cnidarin 4A (1), showed no mammalian cell toxicity or hemolytic activity, which may suggest a role for these cyclic tetraglutamates in nematocyst discharge.
KW  - Animals
KW  - Aquatic Organisms: chemistry
KW  - Cell Death: drug effects
KW  - Chromatography, High Pressure Liquid
KW  - Chromatography, Reverse-Phase
KW  - Cnidarian Venoms: chemistry
KW  - Cnidarian Venoms: toxicity
KW  - Cubozoa: chemistry
KW  - Glutamic Acid: biosynthesis
KW  - Glutamic Acid: chemistry
KW  - Glutamic Acid: isolation & purification
KW  - HEK293 Cells
KW  - Hemolysis: drug effects
KW  - Humans
KW  - Proton Magnetic Resonance Spectroscopy
KW  - Tissue Distribution
LB  - PUB:(DE-HGF)16
C6  - pmid:32079282
C2  - pmc:PMC7070617
DO  - DOI:10.3390/molecules25040883
UR  - https://pub.dzne.de/record/151517
ER  -