PnPP-19, a Synthetic and Nontoxic Peptide Designed from a
            <i>Phoneutria nigriventer</i>
            Toxin, Potentiates Erectile Function via NO/cGMP

Silva, Carolina Nunes; Nunes, Kênia Pedrosa; Torres, Fernanda Silva; Cassoli, Juliana S.; Santos, Daniel Moreira dos; Almeida, Flávia De Marco; Matavel, Alessandra; Cruz, Jáder Santos; Santos‐Miranda, Artur; Nunes, Allancer D C; Castro, Carlos H.; Machado-de-Ávila, Ricardo Andrez; Chávez-Olórtegui, Carlos; Stransky, Stephanie; Felicori, Liza; Resende, Jarbas M.; Camargos, Elizabeth Ribeiro da Silva; Borges, Márcia Helena; Cordeiro, Marta N.; Peigneur, Steve; Tytgat, Jan; Lima, Maria Elena de

doi:10.1016/j.juro.2015.06.081

Cited by 39 publications

(51 citation statements)

References 27 publications

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“…Interestingly, the extra Asn-23 residue present in ocellatin-LB2 sequence seems to decrease its antimicrobial potential and the strength of the peptide-membrane interactions in comparison to ocellatin-LB1. In this sense, it seems to be worth in future investigations to promote site-directed substitutions at Asn-23 in ocellatin-F1 sequence in order to improve the biological activities of this peptide series [50]. Naturally, structural and topological information obtained from other biophysical approaches, such as solution and solid-state NMR spectroscopies [46, 51], can be used to gain information about the peptide-membrane interaction process and may give important insights about the amino acid substitutions at position 23, which can easily be performed by solid-phase peptide synthesis.…”

Section: Resultsmentioning

confidence: 99%

Ocellatin peptides from the skin secretion of the South American frog Leptodactylus labyrinthicus (Leptodactylidae): characterization, antimicrobial activities and membrane interactions

Gusmao

Santos

et al. 2017

J Venom Anim Toxins Incl Trop Dis

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BackgroundThe availability of antimicrobial peptides from several different natural sources has opened an avenue for the discovery of new biologically active molecules. To the best of our knowledge, only two peptides isolated from the frog Leptodactylus labyrinthicus, namely pentadactylin and ocellatin-F1, have shown antimicrobial activities. Therefore, in order to explore the antimicrobial potential of this species, we have investigated the biological activities and membrane interactions of three peptides isolated from the anuran skin secretion.MethodsThree peptide primary structures were determined by automated Edman degradation. These sequences were prepared by solid-phase synthesis and submitted to activity assays against gram-positive and gram-negative bacteria and against two fungal strains. The hemolytic properties of the peptides were also investigated in assays with rabbit blood erythrocytes. The conformational preferences of the peptides and their membrane interactions have been investigated by circular dichroism spectroscopy and liposome dye release assays.ResultsThe amino acid compositions of three ocellatins were determined and the sequences exhibit 100% homology for the first 22 residues (ocellatin-LB1 sequence). Ocellatin-LB2 carries an extra Asn residue and ocellatin-F1 extra Asn-Lys-Leu residues at C-terminus. Ocellatin-F1 presents a stronger antibiotic potential and a broader spectrum of activities compared to the other peptides. The membrane interactions and pore formation capacities of the peptides correlate directly with their antimicrobial activities, i.e., ocellatin-F1 > ocellatin-LB1 > ocellatin-LB2. All peptides acquire high helical contents in membrane environments. However, ocellatin-F1 shows in average stronger helical propensities.ConclusionsThe obtained results indicate that the three extra amino acid residues at the ocellatin-F1 C-terminus play an important role in promoting stronger peptide-membrane interactions and antimicrobial properties. The extra Asn-23 residue present in ocellatin-LB2 sequence seems to decrease its antimicrobial potential and the strength of the peptide-membrane interactions.Electronic supplementary materialThe online version of this article (doi:10.1186/s40409-017-0094-y) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

Ocellatin peptides from the skin secretion of the South American frog Leptodactylus labyrinthicus (Leptodactylidae): characterization, antimicrobial activities and membrane interactions

Gusmao

Santos

et al. 2017

J Venom Anim Toxins Incl Trop Dis

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“…For instance, PnTx3-3 (ω ctenitoxin Pn2a) and Phα1β induce an antinociceptive effect in neuropathic pain models [4, 5]. More recently, we have shown that the synthetic peptide, PnPP-19, firstly characterized as a potentiator of erectile function, also produces antinociception in rats when peripherally injected [1, 17]. We also showed that this peripheral effect involves inhibition of neutral endopeptidase (NEP) (EC 3.4.24.11), and activation of CB 1 , μ- and δ-opioid receptors [17].…”

Section: Discussionmentioning

confidence: 99%

“…PnPP-19 is a synthetic peptide that contains 19 amino acid residues [1]. It represents a part of the primary structure of the native toxin PnTx2-6, also known as δ-ctenitoxin-Pn2a [2], which was isolated from the venom of the spider Phoneutria nigriventer [3].…”

Section: Introductionmentioning

confidence: 99%

A spider derived peptide, PnPP-19, induces central antinociception mediated by opioid and cannabinoid systems

Pacheco

Freitas

Pimenta

et al. 2016

J Venom Anim Toxins Incl Trop Dis

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BackgroundSome peptides purified from the venom of the spider Phoneutria nigriventer have been identified as potential sources of drugs for pain treatment. In this study, we characterized the antinociceptive effect of the peptide PnPP-19 on the central nervous system and investigated the possible involvement of opioid and cannabinoid systems in its action mechanism.MethodsNociceptive threshold to thermal stimulation was measured according to the tail-flick test in Swiss mice. All drugs were administered by the intracerebroventricular route.ResultsPnPP-19 induced central antinociception in mice in the doses of 0.5 and 1 μg. The non-selective opioid receptor antagonist naloxone (2.5 and 5 μg), μ-opioid receptor antagonist clocinnamox (2 and 4 μg), δ-opioid receptor antagonist naltrindole (6 and 12 μg) and CB1 receptor antagonist AM251 (2 and 4 μg) partially inhibited the antinociceptive effect of PnPP-19 (1 μg). Additionally, the anandamide amidase inhibitor MAFP (0.2 μg), the anandamide uptake inhibitor VDM11 (4 μg) and the aminopeptidase inhibitor bestatin (20 μg) significantly enhanced the antinociception induced by a low dose of PnPP-19 (0.5 μg). In contrast, the κ-opioid receptor antagonist nor-binaltorphimine (10 μg and 20 μg) and the CB2 receptor antagonist AM630 (2 and 4 μg) do not appear to be involved in this effect.ConclusionsPnPP-19-induced central antinociception involves the activation of CB1 cannabinoid, μ- and δ-opioid receptors. Mobilization of endogenous opioids and cannabinoids might be required for the activation of those receptors, since inhibitors of endogenous substances potentiate the effect of PnPP-19. Our results contribute to elucidating the action of the peptide PnPP-19 in the antinociceptive pathway.

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“…Importantly, these compounds seemed to preferentially aim at testicles and penis [76] but at a site different from that targeted by sildenafil (Viagra ® ) [81]. Notably, intraperitoneal injection of PnTx2-6 induced priapism in laboratory mice at doses that avoided most of the systemic toxic symptoms [84], and attempts to synthesize analogues with retained erectogenic effect but minimal side effects gave promising results [78,85]. Still, further studies are necessary to evaluate the safety of these compounds as drugs for human use.…”

Section: Cheliceratamentioning

confidence: 99%

Exploring the global animal biodiversity in the search for new drugs – Spiders, scorpions, horseshoe crabs, sea spiders, centipedes, and millipedes

Mans¹

2017

J Transl Sci

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Drug discovery and development programs have historically mainly focused on plants with medicinal properties and the extensive knowledge of traditional healers about these plants. More recently, the vast array of marine invertebrates and insects throughout the world have been recognized as additional sources for identifying unusual lead compounds to obtain structurally novel and mechanistically unique therapeutics. The results from these efforts are encouraging and have yielded a number of clinically useful drugs. However, many arthropods other than insects -such as spiders, scorpions, horseshoe crabs, sea spiders, centipedes, and millipedes -also produce hundreds of bioactive substances in their venom that may become useful in the clinic. Many of these chemicals are defensive and predatory weapons of these creatures and have been refined during millions of years of evolution to rapidly and with high specificity and high affinity shut down critical molecular targets in prey and predators. Exploration of these compounds may lead to the development of, among others, novel drugs for treating diseases caused by abnormalities in humans in the same (evolutionary conserved) molecular targets such as erectyle dysfunction, botulism, and autoimmune disorders, as well as the identification of novel antineoplastic, antimicrobial, and antiparasitic compounds. This paper addresses the importance of bioactive compounds from spiders, scorpions, horseshoe crabs, sea spiders, centipedes, and millipedes to these advances.

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PnPP-19, a Synthetic and Nontoxic Peptide Designed from a Phoneutria nigriventer Toxin, Potentiates Erectile Function via NO/cGMP

Cited by 39 publications

References 27 publications

Ocellatin peptides from the skin secretion of the South American frog Leptodactylus labyrinthicus (Leptodactylidae): characterization, antimicrobial activities and membrane interactions

Ocellatin peptides from the skin secretion of the South American frog Leptodactylus labyrinthicus (Leptodactylidae): characterization, antimicrobial activities and membrane interactions

A spider derived peptide, PnPP-19, induces central antinociception mediated by opioid and cannabinoid systems

Exploring the global animal biodiversity in the search for new drugs – Spiders, scorpions, horseshoe crabs, sea spiders, centipedes, and millipedes

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