Dinogunellins A-D: Putative ichthyootoxic phospholipids of northern blenny Stichaeus grigorjewi eggs

Abstract

Dinogunellins A-D, ichthyootoxic phospholipids, have been isolated from the mature eggs of the northern blenny Stichaeus grigorjewi. Their structures were determined based on spectral and chemical methods as a mixture of 2'-or 3'-acylated adenosine 5'-phosphate linked to the α-carboxyl group of L-asparagine through a P-N bond. and named dinogunellins A-D (2-5). Surprisingly, their structures differed from that proposed in the earlier work. This paper describes the isolation and structure determination of these four new compounds. RESULTS AND DISCUSSIONThe frozen eggs (300 g, wet weight) of S. grigorjewi were homogenized and extracted with CHCl 3 /MeOH (2:1). The CHCl 3 layer obtained after solvent partitioning was purified by silica gel column chromatography and reverse-phase high-performance liquid chromatography (HPLC) to obtain dinogunellins A-D. However, the isolated dinogunellin A (2) gave two peaks corresponding to dinogunellins A and B when analyzed by HPLC, whereas dinogunellin B (3) also gave two peaks corresponding to dinogunellins A and B (Fig. 1). Dinogunellins C and D showed the similar feature. Therefore, it was concluded that dinogunellins A and B as well as dinogunellins C and D were interconvertible to each other. The mixture of dinogunellins A and B was further purified by HPLC using a gel-filtration column to afford a mixture of dinogunellins A and B (41.3 mg, 13.8 × 10 -3 % yield based on wet wt), while 3.3 mg of the mixture of dinogunellins C and D (1.1 × 10 -3 %) was similarly prepared.

Egg toxic compounds in the animal kingdom. A comprehensive review

“…As actin-polymerization inhibitors, macrolides interfere with cytoskeleton functions, eventually leading to cell death. 242,243 They also inhibit protein synthesis by binding to mitochondrial ribosomes, causing cell arrest, 244 further contributing to their cytotoxicity. No toxicity assays have been made at wholeorganism levels and further analyses are needed to determine the role of these toxins in defense against predation.…”

“…[270][271][272][273] Since then, dinogunellin was also found in another blenny sh Stichaeus nozawae, and the killish Fundulus heteroclitus (cyprinodontiformes: fundulidae). 274 In a study on the dinogunellin structure of Stichaeus grigorjewi eggs, four forms of the molecule were identi-ed, named dinogunellin-A, B, C, and D. 242 The site of production and mechanism of transfer to the eggs remain unexplored. If ingested, dinogunellin is toxic to mice and guinea pigs, causing illness and death.…”

Natural Products Containing ‘Rare’ Organophosphorus Functional Groups

“…The distinctive presence of a phosphoramidate P–N bond in dinogunellins is a recurring chemical feature that is widely shared among many nucleotidic antibiotics, e.g., phosmidosines, the antifungal nucleotide antibiotics from Streptomyces durhameusis (see below) [ 270 , 271 ]. In mature eggs of several fish dinogunellins occur as a lipoproteins, complexed with the egg protein vitellogenin [ 272 ]. Interestingly they are absent in immature eggs.…”

Species identification of Cyprinidae fish in Taiwan by FINS and PCR–RFLP analysis

“…Although not as toxic as tetrodotoxin (TTX), dinogunellin can cause gastrointestinal distress, including nausea, vomiting, abdominal pain and diarrhea. Severe symptoms can even lead to death (Asano & Itoh, 1962;Hashimoto, 1979;Matsunaga, Takahashi, & Fusetani, 2009). Previous reports have indicated that some cases of food poisoning in China and Japan are caused by consumption of roe containing dinogunellin (Asano & Itoh, 1962).…”