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Your search keyword '"Cristoval Urcino"' showing total 3 results
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3 results on '"Cristoval Urcino"'

1. Using Constellation Pharmacology to Characterize a Novel α-Conotoxin from Conus ateralbus

Author

Jorge L. B. Neves, Cristoval Urcino, Kevin Chase, Cheryl Dowell, Arik J. Hone, David Morgenstern, Victor M. Chua, Iris Bea L. Ramiro, Julita S. Imperial, Lee S. Leavitt, Jasmine Phan, Fernando A. Fisher, Maren Watkins, Shrinivasan Raghuraman, Jortan O. Tun, Beatrix M. Ueberheide, J. Michael McIntosh, Vitor Vasconcelos, Baldomero M. Olivera, and Joanna Gajewiak

Subjects
conotoxin, nAChRs, Constellation Pharmacology, DRG neurons, Biology (General), QH301-705.5
Abstract

The venom of cone snails has been proven to be a rich source of bioactive peptides that target a variety of ion channels and receptors. α-Conotoxins (αCtx) interact with nicotinic acetylcholine receptors (nAChRs) and are powerful tools for investigating the structure and function of the various nAChR subtypes. By studying how conotoxins interact with nAChRs, we can improve our understanding of these receptors, leading to new insights into neurological diseases associated with nAChRs. Here, we describe the discovery and characterization of a novel conotoxin from Conus ateralbus, αCtx-AtIA, which has an amino acid sequence homologous to the well-described αCtx-PeIA, but with a different selectivity profile towards nAChRs. We tested the synthetic αCtx-AtIA using the calcium imaging-based Constellation Pharmacology assay on mouse DRG neurons and found that αCtx-AtIA significantly inhibited ACh-induced calcium influx in the presence of an α7 positive allosteric modulator, PNU-120596 (PNU). However, αCtx-AtIA did not display any activity in the absence of PNU. These findings were further validated using two-electrode voltage clamp electrophysiology performed on oocytes overexpressing mouse α3β4, α6/α3β4 and α7 nAChRs subtypes. We observed that αCtx-AtIA displayed no or low potency in blocking α3β4 and α6/α3β4 receptors, respectively, but improved potency and selectivity to block α7 nAChRs when compared with αCtx-PeIA. Through the synthesis of two additional analogs of αCtx-AtIA and subsequent characterization using Constellation Pharmacology, we were able to identify residue Trp18 as a major contributor to the activity of the peptide.

Published
2024
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2. Discovery of a Potent Conorfamide from Conus episcopatus Using a Novel Zebrafish Larvae Assay

Author

Kevin Chase, Helena Safavi-Hemami, Joanna Gajewiak, Shrinivasan Raghuraman, Paula Flórez Salcedo, Cristoval Urcino, Randall T. Peterson, Baldomero M. Olivera, Samuel S. Espino, Maren Watkins, Sabrina Kozel, Gabriel D. Bossé, and April Cabang

Subjects
Pharmacology, Conus episcopatus, biology, 010405 organic chemistry, Bioactive molecules, fungi, Organic Chemistry, Pharmaceutical Science, Computational biology, biology.organism_classification, 01 natural sciences, In vitro, 0104 chemical sciences, Analytical Chemistry, Cone snail, Conorfamide, 010404 medicinal & biomolecular chemistry, Complementary and alternative medicine, In vivo, Drug Discovery, Zebrafish larvae, Molecular Medicine, Conotoxin
Abstract

Natural products such as conotoxins have tremendous potential as tools for biomedical research and for the treatment of different human diseases. Conotoxins are peptides present in the venoms of predatory cone snails that have a rich diversity of pharmacological functions. One of the major bottlenecks in natural products research is the rapid identification and evaluation of bioactive molecules. To overcome this limitation, we designed a set of light-induced behavioral assays in zebrafish larvae to screen for bioactive conotoxins. We used this screening approach to test several unique conotoxins derived from different cone snail clades and discovered that a conorfamide from Conus episcopatus, CNF-Ep1, had the most dramatic alterations in the locomotor behavior of zebrafish larvae. Interestingly, CNF-Ep1 is also bioactive in several mouse assay systems when tested in vitro and in vivo. Our novel screening platform can thus accelerate the identification of bioactive marine natural products, and the first compound discovered using this assay has intriguing properties that may uncover novel neuronal circuitry.

Published
2021
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3. Discovery of a Potent Conorfamide from

Author

Gabriel D, Bosse, Cristoval, Urcino, Maren, Watkins, Paula, Flórez Salcedo, Sabrina, Kozel, Kevin, Chase, April, Cabang, Samuel S, Espino, Helena, Safavi-Hemami, Shrinivasan, Raghuraman, Baldomero M, Olivera, Randall T, Peterson, and Joanna, Gajewiak

Subjects
Male, Mice, Larva, Neuropeptides, Conus Snail, Animals, Mollusk Venoms, Female, Locomotion, Zebrafish
Abstract

Natural products such as conotoxins have tremendous potential as tools for biomedical research and for the treatment of different human diseases. Conotoxins are peptides present in the venoms of predatory cone snails that have a rich diversity of pharmacological functions. One of the major bottlenecks in natural products research is the rapid identification and evaluation of bioactive molecules. To overcome this limitation, we designed a set of light-induced behavioral assays in zebrafish larvae to screen for bioactive conotoxins. We used this screening approach to test several unique conotoxins derived from different cone snail clades and discovered that a conorfamide from

Published
2021

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