menu.header.image.unacom.logo
 

Journal Articles

Permanent URI for this collectionhttps://repository.unesco.gov.ph/handle/123456789/50

Browse

Filters

20242

Settings

AGROVOC Keyword: search.filters.agrovoc.marine molluscsSDG: search.filters.sdg.SDG 3 - Good health and well-being

Search Results

Now showing 1 - 2 of 2
  • Thumbnail Image
    Using constellation pharmacology to characterize a novel α-conotoxin from Conus ateralbus
    Neves, Jorge L. B.; Urcino, Cristoval; Chase, Kevin; Dowell, Cheryl; Hone, Arik J.; Morgenstern, David; Chua, Victor M.; Ramiro, Iris Bea L.; Imperial, Julita S.; Leavitt, Lee S.; Phan, Jasmine; Fisher, Fernando A.; Watkins, Maren; Raghuraman, Shrinivasan; Tun, Jortan O.; Ueberheide, Beatrix M.; McIntosh, J. Michael; Vasconcelos, Vitor; Olivera, Baldomero M.; Gajewiak, Joanna (MDPI, 2024-02-29)
    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.
  • No Thumbnail Available
    Diversity and novelty of venom peptides from Conus (Asprella) rolani revealed by analysis of its venom duct transcriptome
    Taguchi, Ryoichi; Masacupan, Dan Jethro; Lluisma, Arturo (Philippine-American Academy of Science and Engineering, 2024-04-22)
    Conus species in the sub-genus Asprella are poorly studied because they inhabit deep-water habitats. To date, only a few peptides have been characterized from this clade. In this study, the venom duct transcriptome of a member of this clade, Conus rolani, was mined for potential conopeptides. Using a highthroughput RNA sequencing platform (Illumina) and a multiple k-mer de novo assembly, we found 103 putative conopeptide precursor amino acid sequences, including the few peptides previously reported for this species. The sequences, predominantly novel based on amino acid sequence, were diverse, comprising 36 gene superfamilies (including the “unassigned” superfamilies). As observed in other Conus species, the O1 gene superfamily was the most diverse (12 distinct sequences) but interestingly none of the sequences were found to contain the conserved amino acids associated with certain bioactivities in peptides found in piscivorous Conus species. The O2 superfamily was also highly diverse but conikot-ikot and an unassigned superfamily (MMSRMG) were more diverse than the rest of the superfamilies. In terms of gene expression levels, the understudied MEFRR paralog of the ancestral divergent M---L-LTVA superfamily was found to be the most highly expressed in the transcriptome, suggesting a novel role. Additionally, a conopeptide with high sequence similarity to A2 secretory group XII phospholipases is the first reported member of this phospholipase group in Conus and potentially represents a novel superfamily, expanding the catalog of known phospholipases present in cone snail venoms. The discovery of these putative conopeptides provides the first but early glimpse of the diversity and novelty of the peptides in the Asprella group and sets the stage for their functional characterization.