title: Novel Conopeptides of Largely Unexplored Indo Pacific Conus sp.
abstract: Cone snails are predatory creatures using venom as a weapon for prey capture and defense. Since this venom is neurotoxic, the venom gland is considered as an enormous collection of pharmacologically interesting compounds having a broad spectrum of targets. As such, cone snail peptides represent an interesting treasure for drug development. Here, we report five novel peptides isolated from the venom ofConus longurionis,Conus asiaticusandConus australis. Lo6/7a and Lo6/7b were retrieved fromC. longurionisand have a cysteine framework VI/VII. Lo6/7b has an exceptional amino acid sequence because no similar conopeptide has been described to date (similarity percentage <50%). A third peptide, Asi3a fromC. asiaticus, has a typical framework III Cys arrangement, classifying the peptide in the M-superfamily. Asi14a, another peptide ofC. asiaticus, belongs to framework XIV peptides and has a unique amino acid sequence. Finally, AusB is a novel conopeptide fromC. australis. The peptide has only one disulfide bond, but is structurally very different as compared to other disulfide-poor peptides. The peptides were screened on nAChRs, NaVand KVchannels depending on their cysteine framework and proposed classification. No targets could be attributed to the peptides, pointing to novel functionalities. Moreover, in the quest of identifying novel pharmacological targets, the peptides were tested for antagonistic activity against a broad panel of Gram-negative and Gram-positive bacteria, as well as two yeast strains.
authors: Toxicology and Pharmacology, KU Leuven, Campus Gasthuisberg, O & N2, Herestraat 49, P.O. Box 922, 3000 Leuven, Belgium. eline.lebbe@pharm.kuleuven.be.
authors: Eline K M
authors: EK
authors: Lebbe
authors: Centre of Microbial and Plant Genetics, KU Leuven, Kasteelpark Arenberg 20, P.O. Box 2460, 3001 Heverlee, Belgium. maarten.ghequire@biw.kuleuven.be.
authors: Maarten G K
authors: MG
authors: Ghequire
authors: Toxicology and Pharmacology, KU Leuven, Campus Gasthuisberg, O & N2, Herestraat 49, P.O. Box 922, 3000 Leuven, Belgium. steve.peigneur@pharm.kuleuven.be.
authors: Steve
authors: S
authors: Peigneur
authors: Toxicology and Pharmacology, KU Leuven, Campus Gasthuisberg, O & N2, Herestraat 49, P.O. Box 922, 3000 Leuven, Belgium. bea.mille@vib-kuleuven.be.
authors: Bea G
authors: BG
authors: Mille
authors: CSIR-National Institute of Oceanography, 403 004 Dona Paula, Goa, India. dprabha@nio.org.
authors: Prabha
authors: P
authors: Devi
authors: Center of Advanced Study in Marine Biology, Annamalai University, 608 502 Parangipettai, Tamil Nadu, India. sravicas@gmail.com.
authors: Samuthirapandian
authors: S
authors: Ravichandran
authors: Laboratory for Protein Phosphorylation and Proteomics, KU Leuven, O & N1 Herestraat 49, P.O. Box 901, 3000 Leuven, Belgium. etienne.waelkens@med.kuleuven.be.
authors: Etienne
authors: E
authors: Waelkens
authors: CSIR-National Institute of Oceanography, 403 004 Dona Paula, Goa, India. lisette@nio.org.
authors: Lisette
authors: L
authors: D'Souza
authors: Centre of Microbial and Plant Genetics, KU Leuven, Kasteelpark Arenberg 20, P.O. Box 2460, 3001 Heverlee, Belgium. rene.demot@biw.kuleuven.be.
authors: René
authors: R
authors: De Mot
authors: Toxicology and Pharmacology, KU Leuven, Campus Gasthuisberg, O & N2, Herestraat 49, P.O. Box 922, 3000 Leuven, Belgium. jan.tytgat@pharm.kuleuven.be.
authors: Jan
authors: J
authors: Tytgat
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000935:Antifungal Agents / Q000494:pharmacology; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D020916:Conotoxins / Q000737:chemistry* / Q000494:pharmacology*; D052078:Conus Snail / Q000737:chemistry*; D004220:Disulfides / Q000737:chemistry; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D008978:Mollusk Venoms / Q000737:chemistry* / Q000494:pharmacology*; D009865:Oocytes; D010140:Pacific Ocean; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D026941:Sodium Channel Blockers / Q000494:pharmacology; D014981:Xenopus; D015003:Yeasts / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D002800:Cholinesterase Inhibitors; D020916:Conotoxins; D004220:Disulfides; D008978:Mollusk Venoms; D010455:Peptides; D026902:Potassium Channel Blockers; D026941:Sodium Channel Blockers
keywords: Conus; antimicrobial tests; conotoxin; electrophysiology; peptide characterization