Isolation, Structure Determination, and Synthesis of Cyclic Tetraglutamic Acids from Box Jellyfish Species <i>Alatina alata</i> and <i>Chironex yamaguchii</i>
Justin Reinicke,
Ryuju Kitatani,
Shadi Sedghi Masoud,
Kelly Kawabata Galbraith,
Wesley Yoshida,
Ayako Igarashi,
Kazuo Nagasawa,
Gideon Berger,
Angel Yanagihara,
Hiroshi Nagai,
F. David Horgen
Affiliations
Justin Reinicke
Department of Natural Sciences, Hawaii Pacific University, Kaneohe, HI 96744, USA
Ryuju Kitatani
Department of Marine Sciences, Tokyo University of Marine Science and Technology, Tokyo 108-8477, Japan
Shadi Sedghi Masoud
Department of Biotechnology and Life Science, Tokyo University of Agriculture and Technology, Tokyo 184-8588, Japan
Kelly Kawabata Galbraith
Department of Natural Sciences, Hawaii Pacific University, Kaneohe, HI 96744, USA
Wesley Yoshida
Department of Chemistry, University of Hawaii at Manoa, Honolulu, HI 98622, USA
Ayako Igarashi
Department of Marine Sciences, Tokyo University of Marine Science and Technology, Tokyo 108-8477, Japan
Kazuo Nagasawa
Department of Biotechnology and Life Science, Tokyo University of Agriculture and Technology, Tokyo 184-8588, Japan
Gideon Berger
Department of Natural Sciences, Hawaii Pacific University, Kaneohe, HI 96744, USA
Angel Yanagihara
Békésy Laboratory of Neurobiology, Pacific Biosciences Research Center, School of Ocean and Earth Science and Technology, and Department of Tropical Medicine, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI 96822, USA
Hiroshi Nagai
Department of Marine Sciences, Tokyo University of Marine Science and Technology, Tokyo 108-8477, Japan
F. David Horgen
Department of Natural Sciences, Hawaii Pacific University, Kaneohe, HI 96744, USA
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.
