Merck
  • Home
  • Search Results
  • In vivo efficacy of anuran trypsin inhibitory peptides against staphylococcal skin infection and the impact of peptide cyclization.

In vivo efficacy of anuran trypsin inhibitory peptides against staphylococcal skin infection and the impact of peptide cyclization.

Antimicrobial agents and chemotherapy (2015-01-28)
U Malik, O N Silva, I C M Fensterseifer, L Y Chan, R J Clark, O L Franco, N L Daly, D J Craik
ABSTRACT

Staphylococcus aureus is a virulent pathogen that is responsible for a wide range of superficial and invasive infections. Its resistance to existing antimicrobial drugs is a global problem, and the development of novel antimicrobial agents is crucial. Antimicrobial peptides from natural resources offer potential as new treatments against staphylococcal infections. In the current study, we have examined the antimicrobial properties of peptides isolated from anuran skin secretions and cyclized synthetic analogues of these peptides. The structures of the peptides were elucidated by nuclear magnetic resonance (NMR) spectroscopy, revealing high structural and sequence similarity with each other and with sunflower trypsin inhibitor 1 (SFTI-1). SFTI-1 is an ultrastable cyclic peptide isolated from sunflower seeds that has subnanomolar trypsin inhibitory activity, and this scaffold offers pharmaceutically relevant characteristics. The five anuran peptides were nonhemolytic and noncytotoxic and had trypsin inhibitory activities similar to that of SFTI-1. They demonstrated weak in vitro inhibitory activities against S. aureus, but several had strong antibacterial activities against S. aureus in an in vivo murine wound infection model. pYR, an immunomodulatory peptide from Rana sevosa, was the most potent, with complete bacterial clearance at 3 mg · kg(-1). Cyclization of the peptides improved their stability but was associated with a concomitant decrease in antimicrobial activity. In summary, these anuran peptides are promising as novel therapeutic agents for treating infections from a clinically resistant pathogen.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Hydrochloric acid solution, ~6 M in H2O, for amino acid analysis
Supelco
Hydrochloric acid solution, volumetric, 0.1 M HCl (0.1N), endotoxin free
Sigma-Aldrich
Sodium pyruvate, BioXtra, ≥99%
Sigma-Aldrich
Hydrochloric acid solution, 1.0 N, BioReagent, suitable for cell culture
Sigma-Aldrich
Hydrochloric acid, 36.5-38.0%, BioReagent, for molecular biology
Sigma-Aldrich
Nα-Benzoyl-L-arginine 4-nitroanilide hydrochloride, >98% (TLC)
Sigma-Aldrich
Nα-Benzoyl-L-arginine 4-nitroanilide hydrochloride, ≥99% (TLC), suitable for substrate for trypsin
Sigma-Aldrich
N,N-Dimethylformamide, for molecular biology, ≥99%
Sigma-Aldrich
Sodium pyruvate, Hybri-Max, powder, suitable for hybridoma
Sigma-Aldrich
Sodium pyruvate, ReagentPlus®, ≥99%
Sigma-Aldrich
N,N-Dimethylformamide, anhydrous, 99.8%
Sigma-Aldrich
Hydrogen chloride solution, 3 M in cyclopentyl methyl ether (CPME)
Sigma-Aldrich
Sodium pyruvate, powder, BioXtra, suitable for mouse embryo cell culture
Sigma-Aldrich
Sodium pyruvate, powder, BioReagent, suitable for cell culture, suitable for insect cell culture, ≥99%
Sigma-Aldrich
Sodium pyruvate, Vetec, reagent grade, 98%
Sigma-Aldrich
Hydrochloric acid solution, 32 wt. % in H2O, FCC
Sigma-Aldrich
Sodium pyruvate, anhydrous, free-flowing, Redi-Dri, ReagentPlus®, ≥99%
Sigma-Aldrich
Deuterium oxide, "100%", 99.990 atom % D
Sigma-Aldrich
Deuterium oxide, standard, 99.98 atom %±0.01 atom % D
Sigma-Aldrich
Deuterium oxide, 99.9 atom % D, contains 1 % (w/w) 3-(trimethylsilyl)-1-propanesulfonic acid, sodium salt (DSS)
Sigma-Aldrich
Deuterium oxide, 99.9 atom % D, contains 0.75 wt. % 3-(trimethylsilyl)propionic-2,2,3,3-d4 acid, sodium salt
Sigma-Aldrich
Deuterium oxide, 99.9 atom % D
Sigma-Aldrich
Deuterium oxide, "100%", ≥99.96 atom % D
Sigma-Aldrich
Deuterium oxide, extra, 99.994 atom % D
Sigma-Aldrich
Deuterium oxide, 99.9 atom % D, glass distilled
Sigma-Aldrich
L-Glutamine, BioUltra, ≥99.5% (NT)
SAFC
L-Glutamine
Sigma-Aldrich
L-Glutamine, meets USP testing specifications, suitable for cell culture, 99.0-101.0%, from non-animal source
Sigma-Aldrich
L-Glutamine, γ-irradiated, BioXtra, suitable for cell culture
Sigma-Aldrich
L-Glutamine, ReagentPlus®, ≥99% (HPLC)