title: Purification, Conformational Analysis, and Properties of a Family of Tigerinin Peptides from Skin Secretions of the Crowned Bullfrog Hoplobatrachus occipitalis.
abstract: Four host-defense peptides belonging to the tigerinin family (tigerinin-1O: RICTPIPFPMCY; tigerinin-2O: RTCIPIPLVMC; tigerinin-3O: RICTAIPLPMCL; and tigerinin-4O: RTCIPIPPVCF) were isolated from skin secretions of the African crowned bullfrog Hoplobatrachus occipitalis. In aqueous solution at pH 4.8, the cyclic domain of tigerinin-2O adopts a rigid amphipathic conformation that incorporates a flexible N-terminal tail. The tigerinins lacked antimicrobial (MIC > 100 μM) and hemolytic (LC50 > 500 μM) activities but, at a concentration of 20 μg/mL, significantly (P < 0.05) inhibited production of interferon-γ (IFN-γ) by peritoneal cells from C57BL/6 mice without affecting production of IL-10 and IL-17. Tigerinin-2O and -4O inhibited IFN-γ production at concentrations as low as 1 μg/mL. The tigerinins significantly (P ≤ 0.05) stimulated the rate of insulin release from BRIN-BD11 clonal β-cells without compromising the integrity of the plasma membrane. Tigerinin-1O was the most potent (threshold concentration 1 nM) and the most effective (395% increase over basal rate at a concentration of 1 μM). Tigerinin-4O was the most potent and effective peptide in stimulating the rate of glucagon-like peptide-1 release from GLUTag enteroendocrine cells (threshold concentration 10 nM; 289% increase over basal rate at 1 μM). Tigerinin peptides have potential for development into agents for the treatment of patients with type 2 diabetes.
authors: SAAD Centre for Pharmacy and Diabetes, School of Biomedical Sciences, University of Ulster , Coleraine, U.K.
authors: Christopher M
authors: CM
authors: McLaughlin
authors: Department of Chemical and Geological Sciences and Department of Biomedical Sciences, Biochemistry Unit, University of Cagliari , Cagliari, Italy.
authors: Sandrina
authors: S
authors: Lampis
authors: SAAD Centre for Pharmacy and Diabetes, School of Biomedical Sciences, University of Ulster , Coleraine, U.K.
authors: Milena
authors: M
authors: Mechkarska
authors: CNRS UMR 6270, PISSARO, University of Rouen, Institute for Research and Innovation in Biomedicine (IRIB) , Mont-Saint-Aignan, France.
authors: Laurent
authors: L
authors: Coquet
authors: CNRS UMR 6270, PISSARO, University of Rouen, Institute for Research and Innovation in Biomedicine (IRIB) , Mont-Saint-Aignan, France.
authors: Thierry
authors: T
authors: Jouenne
authors: Rare Species Conservatory Foundation , St. Louis, Missouri, United States.
authors: Jay D
authors: JD
authors: King
authors: Instituto Pasteur-Fondazione Cenci Bolognetti, Department of Biochemical Sciences, Sapienza University of Rome , Rome, Italy.
authors: Maria Luisa
authors: ML
authors: Mangoni
authors: Center for Molecular Medicine, Faculty of Medicine, University of Kragujevac , Kragujevac, Serbia.
authors: Miodrag L
authors: ML
authors: Lukic
authors: Department of Chemical and Geological Sciences and Department of Biomedical Sciences, Biochemistry Unit, University of Cagliari , Cagliari, Italy.
authors: Mariano A
authors: MA
authors: Scorciapino
authors: SAAD Centre for Pharmacy and Diabetes, School of Biomedical Sciences, University of Ulster , Coleraine, U.K.
authors: J Michael
authors: JM
authors: Conlon
mesh_terms: D029845:Amphibian Proteins / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007328:Insulin / Q000494:pharmacology; D016753:Interleukin-10 / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008826:Microbial Sensitivity Tests; D010455:Peptides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D011892:Rana catesbeiana; D012867:Skin / Q000187:drug effects / Q000378:metabolism*
chemical_list: D029845:Amphibian Proteins; D023181:Antimicrobial Cationic Peptides; D007328:Insulin; D020381:Interleukin-17; D010455:Peptides; C469876:tigerinin 1; D016753:Interleukin-10