TY - JOUR
T1 - Purification of peptides with differential cytolytic activities from the skin secretions of the Central American frog, Lithobates vaillanti (Ranidae)
AU - Conlon, John Michael
AU - Raza, Haider
AU - Coquet, Laurent
AU - Jouenne, Thierry
AU - Leprince, Jérôme
AU - Vaudry, Hubert
AU - King, Jay D.
N1 - Funding Information:
This work was supported by a grant from the Terry Fox Fund for Cancer Research and a Faculty Support Grant from UAE University. The authors thank Ms Eman Ahmed and Ms Annie John for technical assistance. The authors also thank Brian Kubicki, Costa Rican Amphibian Research Center for providing frog specimens.
PY - 2009/8
Y1 - 2009/8
N2 - Peptide-based defenses of ranid frogs from Mexico and Central America have been studied in much less detail than those from North America. Peptides belonging to the brevinin-1 (5 peptides), palustrin-2 (1 peptide), and ranatuerin-2 (3 peptides) families were isolated from norepinephrine-stimulated skin secretions of the Costa Rican frog, Lithobates vaillanti (Ranidae) and characterized structurally. Brevinin-1VLa (FLGAIAGVAAKFLPKVFCFITKKC) and brevinin-1VLc (FLPVIASVAAKVLPK VFCFITKKC) showed particularly high growth-inhibitory potency (MIC ≤ 3 μM) against a Gram-positive microorganism Staphylococcus aureus and the opportunistic yeast pathogen Candida albicans and potent cytolytic activity (LC50 ≤ 8 μM) against both human erythrocytes and HepG2 hepatoma-derived cells. The peptides were also active against a Gram-negative microorganism Escherichia coli (MIC ≤ 50 μM). Substitutions in brevinin-1VLd (Lys11 → Asn) and brevinin-1VLe (Lys11 → Ser) that decrease cationicity result in loss of activity against E. coli. Ranatuerin-2VLb (GIMDTIKGAAKDLAGQLLDKLKCKITKC) showed relatively weak antimicrobial activity (MIC ≥ 75 μM) but selective cytolytic activity against HepG2 tumor cells (LC50 = 30 μM) compared with erythrocytes (LC50 > 200 μM). In addition, a dodecapeptide (RICYAMWIPYPC) were isolated from the secretions that were devoid of antimicrobial activity. This component contains an Ala-Met bond that constitutes the scissile bond in the selective elastase inhibitor, elafin but the peptide did not inhibit pancreatic elastase at concentrations up to 100 μM.
AB - Peptide-based defenses of ranid frogs from Mexico and Central America have been studied in much less detail than those from North America. Peptides belonging to the brevinin-1 (5 peptides), palustrin-2 (1 peptide), and ranatuerin-2 (3 peptides) families were isolated from norepinephrine-stimulated skin secretions of the Costa Rican frog, Lithobates vaillanti (Ranidae) and characterized structurally. Brevinin-1VLa (FLGAIAGVAAKFLPKVFCFITKKC) and brevinin-1VLc (FLPVIASVAAKVLPK VFCFITKKC) showed particularly high growth-inhibitory potency (MIC ≤ 3 μM) against a Gram-positive microorganism Staphylococcus aureus and the opportunistic yeast pathogen Candida albicans and potent cytolytic activity (LC50 ≤ 8 μM) against both human erythrocytes and HepG2 hepatoma-derived cells. The peptides were also active against a Gram-negative microorganism Escherichia coli (MIC ≤ 50 μM). Substitutions in brevinin-1VLd (Lys11 → Asn) and brevinin-1VLe (Lys11 → Ser) that decrease cationicity result in loss of activity against E. coli. Ranatuerin-2VLb (GIMDTIKGAAKDLAGQLLDKLKCKITKC) showed relatively weak antimicrobial activity (MIC ≥ 75 μM) but selective cytolytic activity against HepG2 tumor cells (LC50 = 30 μM) compared with erythrocytes (LC50 > 200 μM). In addition, a dodecapeptide (RICYAMWIPYPC) were isolated from the secretions that were devoid of antimicrobial activity. This component contains an Ala-Met bond that constitutes the scissile bond in the selective elastase inhibitor, elafin but the peptide did not inhibit pancreatic elastase at concentrations up to 100 μM.
KW - Antimicrobial peptide
KW - Brevinin-1
KW - Lithobates
KW - Palustrin-2
KW - Ranatuerin-2
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U2 - 10.1016/j.cbpc.2009.04.003
DO - 10.1016/j.cbpc.2009.04.003
M3 - Article
C2 - 19379837
AN - SCOPUS:67649502897
SN - 1532-0456
VL - 150
SP - 150
EP - 154
JO - Comparative Biochemistry and Physiology - C Toxicology and Pharmacology
JF - Comparative Biochemistry and Physiology - C Toxicology and Pharmacology
IS - 2
ER -