Neurotoxic acylpolyamines from spider venoms

McCormick, Kevin D.; Meinwald, Jerrold

doi:10.1007/bf00979674

Cited by 91 publications

(32 citation statements)

References 132 publications

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“…6), which seem to have evolved specifically as tools for paralyzing prey. 4,6,93,94 The first polyamine toxins were found in the venom of tarantula spiders more than 40 years ago, 95 but it took almost 30 years before the first structure of this new class of toxins was characterized. In 1986, Volkova and colleagues isolated and characterized a polyamine toxin from the venom of the orb weaver spider Argiope lobata, designated argiotoxin-636 a (ArgTX-636, 18, Fig.…”

mentioning

confidence: 99%

AMPA receptor ligands: Synthetic and pharmacological studies of polyamines and polyamine toxins

Strømgaard

Mellor

2004

Medicinal Research Reviews

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Alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors (AMPAR), subtype of the ionotropic glutamate receptors (IGRs), mediate fast synaptic transmission in the central nervous system (CNS), and are involved in many neurological disorders, as well as being a key player in the formation of memory. Hence, ligands affecting AMPARs are highly important for the study of the structure and function of this receptor, and in this regard polyamine-based ligands, particularly polyamine toxins, are unique as they selectively block Ca2+ -permeable AMPARs. Indeed, endogenous intracellular polyamines are known to modulate the function of these receptors in vivo. In this study, recent developments in the medicinal chemistry of polyamine-based ligands are given, particularly focusing on the use of solid-phase synthesis (SPS) as a tool for the facile generation of libraries of polyamine toxin analogues. Moreover, the recent development of highly potent and very selective AMPAR ligands is described. Additionally, we provide a detailed account on the mechanism and site of action of AMPAR blockade by polyamine-based ligands, including examples of how these ligands are used as tools to study AMPAR, and a comparison with their action on other ionotropic receptors.

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confidence: 99%

AMPA receptor ligands: Synthetic and pharmacological studies of polyamines and polyamine toxins

Strømgaard

Mellor

2004

Medicinal Research Reviews

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“…Like many of the venoms investigated, C. pastoralis venom was found to contain significant amounts of acylated polyamines, a large family of natural products that has been extensively studied (7). The presence of acyl polyamines in our unpurified venoms was easily recognized based on the characteristic spin systems of their aromatic head groups, whose connections to the polyamine chains were evident from the HMBC spectra.…”

Section: Resultsmentioning

confidence: 86%

“…1) (5). Except for a single example (6), sulfated nucleosides had completely escaped detection by conventional isolation and characterization protocols, although spider venoms had been subject to intensive chemical scrutiny that had led to identification of hundreds of proteins, peptides, acylated polyamines, and various small-molecule neurotransmitters (7,8).…”

mentioning

confidence: 99%

NMR-spectroscopic screening of spider venom reveals sulfated nucleosides as major components for the brown recluse and related species

Schroeder

Taggi²,

Gronquist

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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Extensive chemical analyses of spider venoms from many species have revealed complex mixtures of biologically active compounds, of which several have provided important leads for drug development. We have recently shown that NMR spectroscopy can be used advantageously for a direct structural characterization of the small-molecule content of such complex mixtures. Here, we report the application of this strategy to a larger-scale analysis of a collection of spider venoms representing >70 species, which, in combination with mass spectrometric analyses, allowed the identification of a wide range of known, and several previously undescribed, small molecules. These include polyamines, common neurotransmitters, and amino acid derivatives as well as two additional members of a recently discovered family of natural products, the sulfated nucleosides. In the case of the well studied brown recluse spider, Loxosceles reclusa, sulfated guanosine derivatives were found to comprise the major small-molecule components of the venom. chemical prospecting ͉ Loxosceles ͉ metabolomics ͉ natural products ͉ neurotoxins

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“…It is of particular interest that polyamines closely related to CNS 2103 have been found not only in other spider species (29) but also in the venom of the solitary digger wasp Philanthus triangulum (32). The similarity of these wasp and spider neurotoxins provides a notable example of convergence in the evolution of secondary metabolites aimed at a common target.…”

Section: Desoxycorticosteronementioning

confidence: 99%

The chemistry of phyletic dominance.

Meinwald

Eisner

1995

Proc. Natl. Acad. Sci. U.S.A.

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Studies of arthropod defensive chemistry continue to bring to light novel structures and unanticipated biosynthetic capabilities. Insect alkaloids, such as the heptacyclic acetogenin chilocorine and the azamacrolides, exemplify both of these aspects of arthropod chemistry. Spider venoms are proving to be rich sources of neuroactive components of potential medical interest. The venom of a fishing spider, Dolomedes okefinokensis, has yielded a polyamine which reversibly blocks L-and R-type voltage-sensitive calcium channels. Most recently, we have characterized, from the funnel-web spider Hololena curta, a sulfated nucleoside glycoside which serves as a reversible blocker of glutamatesensitive calcium channels. The ability to synthesize or acquire an extremely diverse array of compounds for defense, offense, and communication appears to have contributed significantly to the dominant position that insects and other arthropods have attained.

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Neurotoxic acylpolyamines from spider venoms

Cited by 91 publications

References 132 publications

AMPA receptor ligands: Synthetic and pharmacological studies of polyamines and polyamine toxins

AMPA receptor ligands: Synthetic and pharmacological studies of polyamines and polyamine toxins

NMR-spectroscopic screening of spider venom reveals sulfated nucleosides as major components for the brown recluse and related species

The chemistry of phyletic dominance.

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