Relative stereochemistry of pinnatoxin A, a potent shellfish poison from Pinna muricata

Chou, Tong; Kamo, Osamu; Uemura, Daisuke

doi:10.1016/0040-4039(96)00752-6

Cited by 116 publications

(31 citation statements)

References 3 publications

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“…3). Here, this ring system perfectly complements the non-polar environment of the surrounding residues in A-AChBP, and retains the preferred cis stereochemistry elucidated by NMR analysis and confirmed by total synthesis (Chou, 1996; McCauley et al, 1998). As a result, the proximal tetrahydropyran ring (ring D) perfectly abuts against Tyr188, Tyr195 and the vicinal Cys190 and Cys191 (loop C), while the central tetrahydrofuran ring (ring C) does not make direct contacts, and while the distal tetrahydropyran ring (ring B) interacts with Val148 (loop E) from the (−) face.…”

Section: Resultssupporting

confidence: 55%

Marine Macrocyclic Imines, Pinnatoxins A and G: Structural Determinants and Functional Properties to Distinguish Neuronal α7 from Muscle α12βγδ nAChRs

et al. 2015

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Pinnatoxins are macrocyclic imine phycotoxins associated with algal blooms and shellfish toxicity. Functional analysis of pinnatoxin-A and pinnatoxin-G, by binding and electrophysiology on membrane-embedded neuronal α7, α4β2 and α3β2 and muscle-type α12βγδ nicotinic acetylcholine receptors (nAChRs), reveals high-affinity binding and potent antagonism for the α7 and α12βγδ subtypes. The toxins also bind to the nAChR surrogate, acetylcholine-binding protein (AChBP), with low Kd’s reflecting slow dissociation. Crystal structures of pinnatoxin-AChBP complexes (1.9–2.2Å resolution) picture the multiple anchoring points of the hydrophobic portion, the cyclic imine and the substituted bis-spiroketal and cyclohexene ring systems of the pinnatoxins that dictate tight binding between the opposing loops C and F at the receptor subunit interface, as observed for the 13-desmethyl-spirolide-C and gymnodimine-A congeners. Uniquely however, the bulky bridged EF-ketal ring specific to the pinnatoxins extends radially from the interfacial-binding pocket to interact with the sequence-variable loop F and govern nAChR-subtype selectivity and central neurotoxicity.

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Section: Resultssupporting

confidence: 55%

Marine Macrocyclic Imines, Pinnatoxins A and G: Structural Determinants and Functional Properties to Distinguish Neuronal α7 from Muscle α12βγδ nAChRs

et al. 2015

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“…The spectroscopic and mass spectrometric data of the new compounds 4 and 5 and those of tetrahydrotectol (6) are in accordance with the proposed chemical structures. In an exploratory reaction, compounds 4 and 5 were treated with methanol/HCl (g) at room temperature, resulting in high yields of colorless oils.…”

Section: Introductionsupporting

confidence: 71%

“…1,2 For instance, many marine toxins including the spirolides, [3][4][5] pinnatoxins, 6,7 and pteriatoxins 8 are naturally occurring compounds with spirocyclic subunits in their molecular skeleton. The presence of such subunits brings about pertinent challenges in organic synthesis, 2,3,9,10 as in Brimble's 11 recent article reporting the construction of the aromatic spiroketal subunits of rubromycins, a family of antibiotics isolated from Streptomyces's cultures which exhibits activity against Gram-positive bacteria.…”

Section: Introductionmentioning

confidence: 99%

Unexpected transformation of quinones to spirolactones and to naturally occurring naphthalenic compounds

Júnior

Simone

Souza

et al. 2009

Tetrahedron Letters

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“…Pinnatoxins (PnTXs) had initially been isolated from Pinna muricata collected in Japan (Chou et al, 1996a, 1996b; Takada et al, 2001a; Uemura et al, 1995), the same genus of mollusc associated in the early 1990s with a Pinna attenuata poisoning in China. Metabolism pathways were subsequently postulated by Selwood et al (2010) to explain biotransformation of the algal metabolites PnTXs E, F and G into shellfish metabolites PnTXs A, B, C and D and pter-iatoxins A, B and C, initially reported by Hao et al (2006) and Takada et al (2001b).…”

Section: Introductionmentioning

confidence: 99%

Pinnatoxin G is responsible for atypical toxicity in mussels (Mytilus galloprovincialis) and clams (Venerupis decussata) from Ingril, a French Mediterranean lagoon

Heß

Abadie

Hervé

et al. 2013

Toxicon

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Following a review of official control data on shellfish in France, Ingril Lagoon had been identified as a site where positive mouse bioassays for lipophilic toxins had been repeatedly observed. These unexplained mouse bioassays, also called atypical toxicity, coincided with an absence of regulated toxins and rapid death times in mice observed in the assay. The present study describes pinnatoxin G as the main compound responsible for the toxicity observed using the mouse bioassay for lipophilic toxins. Using a well-characterised standard for pinnatoxin G, LC-MS/MS analysis of mussel samples collected from 2009 to 2012 revealed regular occurrences of pinnatoxin G at levels sufficient to account for the toxicity in the mouse bioassays. Baseline levels of pinnatoxin G from May to October usually exceeded 40 µg kg−1 in whole flesh, with a maximum in September 2010 of around 1200 µg kg−1. These concentrations were much greater than those at the other 10 sites selected for vigilance testing, where concentrations did not exceed 10 µg kg−1 in a 3-month survey from April to July 2010, and where rapid mouse deaths were not typically observed. Mussels were always more contaminated than clams, confirming that mussel is a good sentinel species for pinnatoxins. Profiles in mussels and clams were similar, with the concentration of pinnatoxin A less than 2% that of pinnatoxin G, and pteriatoxins were only present in non-quantifiable traces. Esters of pinnatoxin G could not be detected by analysis of extracts before and after alkaline hydrolysis. Analysis with a receptor-binding assay showed that natural pinnatoxin G was similarly active on the nicotinic acetylcholine receptor as chemically synthesized pinnatoxin G. Culture of Vulcanodinium rugosum, previously isolated from Ingril lagoon, confirmed that this alga is a pinnatoxin G producer (4.7 pg cell−1). Absence of this organism from the water column during prolonged periods of shellfish contamination and the dominance of non-motile life stages of V. rugosum both suggest that further studies will be required to fully describe the ecology of this organism and the accumulation of pinnatoxins in shellfish.

show abstract

Relative stereochemistry of pinnatoxin A, a potent shellfish poison from Pinna muricata

Cited by 116 publications

References 3 publications

Marine Macrocyclic Imines, Pinnatoxins A and G: Structural Determinants and Functional Properties to Distinguish Neuronal α7 from Muscle α12βγδ nAChRs

Marine Macrocyclic Imines, Pinnatoxins A and G: Structural Determinants and Functional Properties to Distinguish Neuronal α7 from Muscle α12βγδ nAChRs

Unexpected transformation of quinones to spirolactones and to naturally occurring naphthalenic compounds

Pinnatoxin G is responsible for atypical toxicity in mussels (Mytilus galloprovincialis) and clams (Venerupis decussata) from Ingril, a French Mediterranean lagoon

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