Total Synthesis of the Novel Spider Toxin NPTX-594 from <i>Nephila madagascariencis</i>

Wakamiya, Tateaki; Yamamoto, Akinori; Kawaguchi, Keita; Kinoshita, Takehiko; Yamaguchi, Yoshihiro; Itagaki, Yasuhiro; Naoki, Hideo; Nakajima, Terumi

doi:10.1246/bcsj.74.1743

Cited by 7 publications

(1 citation statement)

References 25 publications

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“…( A. lobata , Araneidae ) and Wakamiya et al . ( Nephila species, Nephilidae ). , They were isolated, and their structures were elucidated by NMR.…”

Section: Resultsmentioning

confidence: 99%

Elucidation of the Structure and Synthesis of Neuroprotective Low Molecular Mass Components of the Parawixia bistriata Spider Venom

Forster

Green

Khatiwada

et al. 2020

ACS Chem. Neurosci.

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The South American social spider Parawixia bistriata produces a venom containing complex organic compounds with intriguing biological activities. The crude venom leads to paralysis in termites and stimulates l-glutamate uptake and inhibits GABA uptake in rat brain synaptosomes. Glutamate is the major neurotransmitter at the insect neuromuscular junction and at the mammalian central nervous system, suggesting a modulation of the glutamatergic system by the venom. Parawixin1, 2, and 10 (Pwx1, 2 and 10) are HPLC fractions that demonstrate this bioactivity. Pwx1 stimulates l-glutamate uptake through the main transporter in the brain, EAAT2, and is neuroprotective in in vivo glaucoma models. Pxw2 inhibits GABA and glycine uptake in synaptosomes and inhibits seizures and neurodegeneration, and Pwx10 increases l-glutamate uptake in synaptosomes and is neuroprotective and anticonvulsant, shown in in vivo epilepsy models. Herein, we investigated the low molecular mass compounds in this venom and have found over 20 small compounds and 36 unique acylpolyamines with and without amino acid linkers. The active substances in fractions Pwx1 and Pwx2 require further investigation. We elucidated and confirmed the structure of the active acylpolyamine in Pwx10. Both fraction Pwx10 and the synthesized component enhance the activity of transporters EAAT1 and EAAT2, and, importantly, offer in vitro neuroprotection against excitotoxicity in primary cultures. These data suggest that compounds with this mechanism could be developed into therapies for disorders in which l-glutamate excitotoxicity is involved.

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“…( A. lobata , Araneidae ) and Wakamiya et al . ( Nephila species, Nephilidae ). , They were isolated, and their structures were elucidated by NMR.…”

Section: Resultsmentioning

confidence: 99%