Untitled

Moe, Scott T.; Smith, Daryl L.; Chien, Yongwei; Raszkiewicz, Joanna L.; Artman, Linda D.; Mueller, Alan L.

doi:10.1023/a:1011988317683

Cited by 18 publications

(5 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This suggests that electrostatic interactions between electropositive sites on the polyamine moiety and complementary sites on the receptor are not the basis for binding of these compounds to nAChR. This is in contrast to the locust muscle qGluR and rat brain NMDA receptor (NMDAR), which may require the presence of the polycationic residues as suggested by the present and previous , results. This substantial difference opens up the possibility of developing philanthotoxin analogues that selectively target different ionotropic receptors.…”

Section: Discussionmentioning

confidence: 46%

Analogues of Neuroactive Polyamine Wasp Toxins That Lack Inner Basic Sites Exhibit Enhanced Antagonism Toward a Muscle-Type Mammalian Nicotinic Acetylcholine Receptor

et al. 1999

View full text Add to dashboard Cite

Philanthotoxin-433 (PhTX-433), a natural polyamine wasp toxin, is a noncompetitive antagonist of certain ionotropic receptors. Six analogues of PhTX-343 (a synthetic analogue of the natural product), in which the secondary amino groups are systematically replaced by oxygen or methylene groups, have been synthesized by coupling of N-(1-oxobutyl)tyrosine with 1,12-dodecanediamine, 4,9-dioxa-1, 12-dodecanediamine, or appropriately protected di- and triamines, the latter being obtained by multistep syntheses. The resulting PhTX-343 analogues were purified and characterized, and their protolytic properties (stepwise macroscopic pK(a) values) were determined by (13)C NMR titrations. All analogues are fully protonated at physiological pH. The effects of these compounds on acetylcholine-induced currents in TE671 cells clamped at various holding potentials were determined. All of the analogues noncompetitively antagonized the nicotinic acetylcholine receptor (nAChR) in a concentration-, time-, and voltage-dependent manner. The amplitudes of acetylcholine-induced currents were compared at their peaks and at the end of a 1 s application in the presence or absence of the analogues. Most of the analogues were equipotent with or more potent than PhTX-343. The dideaza analogue PhTX-12 [IC(50) of 0.3 microM (final current value)] was the most potent, representing the highest potency improvement (about 50-fold) yet achieved by modification of the parent compound (PhTX-343). Thus, the presence of multiple positive charges in the PhTX-343 molecule is not necessary for antagonism of nAChR. In contrast, the compounds were much less potent than PhTX-343 at locust muscle ionotropic glutamate receptors sensitive to quisqualate (qGluR). The results demonstrate that the selectivity for different types of ionotropic receptors can be achieved by manipulating the polyamine moiety of PhTX-343.

show abstract

Section: Discussionmentioning

confidence: 46%

Analogues of Neuroactive Polyamine Wasp Toxins That Lack Inner Basic Sites Exhibit Enhanced Antagonism Toward a Muscle-Type Mammalian Nicotinic Acetylcholine Receptor

et al. 1999

View full text Add to dashboard Cite

show abstract

“…Interestingly, PPAR

activation results in cellular protection from NMDA toxicity [ 27 ]. Given the known inhibitory effect of argiotoxins on NMDA receptors [ 28 ], this is striking and biologically plausible evidence for toxin synergism, where two or more venom components target multiple cellular structures with related functions in order to incite a more powerful response [ 29 ].…”

Section: Resultsmentioning

confidence: 99%

Discovering Venom-Derived Drug Candidates Using Differential Gene Expression

Romano

Napolitano

et al. 2023

Toxins

View full text Add to dashboard Cite

Venoms are a diverse and complex group of natural toxins that have been adapted to treat many types of human disease, but rigorous computational approaches for discovering new therapeutic activities are scarce. We have designed and validated a new platform—named VenomSeq—to systematically identify putative associations between venoms and drugs/diseases via high-throughput transcriptomics and perturbational differential gene expression analysis. In this study, we describe the architecture of VenomSeq and its evaluation using the crude venoms from 25 diverse animal species and 9 purified teretoxin peptides. By integrating comparisons to public repositories of differential expression, associations between regulatory networks and disease, and existing knowledge of venom activity, we provide a number of new therapeutic hypotheses linking venoms to human diseases supported by multiple layers of preliminary evidence.

show abstract

“…The mechanism by which Pwx 10 acts on glutamate transport remains unknown and more studies are required to clarify it. As the Pwx 10, further spider neurotoxins have affinity for receptors and ion channels in the CNS, among them we have the argiotoxin 636, a noncompetitive NMDA antagonist,[ 16 ] JSTX-3 (an analogue of Jorotoxin) that blocks epileptiform activity in both rat hippocampal sections as human. [ 17 ] Some toxins from the spider Phoneutria nigriventer (PhTx-3, TX 3-3, TX 3-4) were neuroprotective in the induction of a model of retinal ischemia[ 18 ] and PhTx-56, an analogue of philantotoxina-433 that acts as potent and selective antagonist of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors[ 19 ] and transport of glutamate by inhibiting its reuptake dose-dependent manner.…”

Section: Discussionmentioning

confidence: 99%

Neuroprotective activity of parawixin 10, a compound isolated from Parawixia bistriata spider venom (Araneidae: Araneae) in rats undergoing intrahippocampal NMDA microinjection

et al. 2015

View full text Add to dashboard Cite

Background:Parawixia bistriata is a semi-colonial spider found mainly in southeastern of Brazil. Parawixin 10 (Pwx 10) a compound isolated from this spider venom has been demonstrated to act as neuroprotective in models of injury regulating the glutamatergic neurotransmission through glutamate transporters.Objectives:The aim of this work was to evaluate the neuroprotective effect of Pwx 10 in a rat model of excitotoxic brain injury by N-methyl-D-aspartate (NMDA) injection.Material and Methods:Male Wistar rats have been used, submitted to stereotaxic surgery for saline or NMDA microinjection into dorsal hippocampus. Two groups of animals were treated with Pwx 10. These treated groups received a daily injection of the Pwx 10 (2.5 mg/μL) in the right lateral ventricle into rats pretreated with NMDA, always at the same time, each one starting the treatment 1 h or 24 h. Nissl staining was performed for evaluating the extension and efficacy of the NMDA injury and the neuroprotective effect of Pwx 10.Results:The treatment with Pwx 10 showed neuroprotective effect, being most pronounced when the compound was administrated from 1 h after NMDA in all hippocampal subfields analyzed (CA1, CA3 and hilus).Conclusion:These results indicated that Pwx 10 may be a good template to develop therapeutic drugs for treating neurodegenerative diseases, reinforcing the importance of continuing studies on its effects in the central nervous system.

show abstract

Untitled

Cited by 18 publications

References 11 publications

Analogues of Neuroactive Polyamine Wasp Toxins That Lack Inner Basic Sites Exhibit Enhanced Antagonism Toward a Muscle-Type Mammalian Nicotinic Acetylcholine Receptor

Analogues of Neuroactive Polyamine Wasp Toxins That Lack Inner Basic Sites Exhibit Enhanced Antagonism Toward a Muscle-Type Mammalian Nicotinic Acetylcholine Receptor

Discovering Venom-Derived Drug Candidates Using Differential Gene Expression

Neuroprotective activity of parawixin 10, a compound isolated from Parawixia bistriata spider venom (Araneidae: Araneae) in rats undergoing intrahippocampal NMDA microinjection

Contact Info

Product

Resources

About