Discovery of a New Analgesic Peptide, Leptucin, from the Iranian Scorpion, Hemiscorpius lepturus

Autor: Jean-Marc Sabatier, Soroush Sardari, Sedigheh Bagheri-Ziari, Delavar Shahbazzadeh, Kamran Pooshang Bagheri
Přispěvatelé: Institut de neurophysiopathologie (INP), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)
Rok vydání: 2021
Předmět:
MESH: Analgesics
leptucin
Analgesic
Pharmaceutical Science
Peptide
Venom
MESH: Amino Acid Sequence
MESH: Spectrum Analysis
Scorpion stings
MESH: Base Sequence
Pharmacology
Analytical Chemistry
03 medical and health sciences
QD241-441
scorpion
MESH: Protein Conformation
In vivo
Drug Discovery
medicine
MESH: Animals
[SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry
Molecular Biology/Biochemistry [q-bio.BM]
Physical and Theoretical Chemistry
MESH: Chromatography
High Pressure Liquid
Cytotoxicity
Hemiscorpius lepturus
030304 developmental biology
chemistry.chemical_classification
0303 health sciences
MESH: Peptides
030302 biochemistry & molecular biology
Organic Chemistry
MESH: Maximum Tolerated Dose
MESH: Open Reading Frames
medicine.disease
MESH: Hemolysis
MESH: Scorpions
3. Good health
chemistry
Chemistry (miscellaneous)
Toxicity
analgesic peptide
MESH: Iran
Molecular Medicine
MESH: Scorpion Stings
Tail flick test
MESH: Computational Biology
Zdroj: Molecules
Molecules, MDPI, 2021, 26 (9), pp.2580. ⟨10.3390/molecules26092580⟩
Volume 26
Issue 9
Molecules, 2021, 26 (9), pp.2580. ⟨10.3390/molecules26092580⟩
Molecules, Vol 26, Iss 2580, p 2580 (2021)
ISSN: 1420-3049
DOI: 10.3390/molecules26092580
Popis: International audience; Hemiscorpius lepturus scorpion stings do not induce considerable pain based on epidemiological surveys conducted in the southwest part of Iran. Accordingly, this study was aimed to identify the analgesic molecule in H. lepturus venom by analyzing a cDNA library of the scorpion venom gland looking for sequences having homology with known animal venom analgesic peptides. The analgesic molecule is a cysteine rich peptide of 55 amino acids. the synthetic peptide was deprotected and refolded. RP-HPLC, Ellman’s, and DLS assays confirmed the refolding accuracy. Circular dichroism (CD) showed helix and beta sheet contents. This peptide, called leptucin, demonstrated 95% analgesic activity at the dose of 0.48 mg/kg in hot plate assay. Leptucin at the doses of 0.32, 0.48, and 0.64 mg/kg showed 100% activity in thermal tail flick test. No hemolysis or cytotoxicity was observed at 8 and 16 μg. Histopathology evaluations indicated no hepatotoxicity, nephrotoxicity, and cardiotoxicity. We thus report that leptucin is the analgesic agent of H. lepturus venom. Regarding the high in vivo efficacy of leptucin and the fact it shows no observable toxicity, it could be suggested as a drug lead in a preclinical study of acute pain as well as the study of its mechanism of action.
Databáze: OpenAIRE
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