Safety Of Peptide Research Articles

Improving the stability of thiol-maleimide bioconjugates via the formation of a thiazine structure.

Linker stability is critically important for the efficacy and safety of peptide and protein conjugates used for biological applications. One common conjugation strategy, thiol-maleimide coupling, generates a succinimidyl thioether linker with limited stability under physiological conditions. We have shown in previous work that when a peptide with an N-terminal cysteine is conjugated to a maleimide reagent, a thiazine structure is formed via a chemical rearrangement. Our preliminary work indicated that the thiazine linker has favorable stability. Here, we report the evaluation of a thiazine linker as an alternative to the widely used succinimidyl thioether linker for thiol-maleimide bioconjugation. The stability of the thiazine conjugate in comparison to the thioether conjugate was assessed across a broad pH range. Additionally, the propensity for retro-Michael reaction and cross-reactivity with other thiols was evaluated by treating conjugates in the presence of glutathione. The studies indicated that the thiazine linker degrades markedly slower than the thioether conjugate. In addition, the thiazine linker is over 20 times less susceptible to glutathione adduct formation. The NMR study of the thiazine structure confirmed that the formation of the thiazine linker is a stereoselective process that yields a single diastereomer. In summary, we propose the use of the thiazine linker obtained by conjugation of maleimide-containing reagents with peptides or proteins presenting an N-terminal cysteine as a novel approach for bioconjugation. The advantages of this approach are the formation of a linker with a well-defined stereochemical configuration, increased stability at physiological pH, and a strongly reduced propensity for thiol exchange.

Study on the characterisation and application of synthetic peptide Snakin-1 derived from potato tubers – Action against food spoilage yeast

The demand for more natural forms of food preservation by consumers has risen in recent years. Food spoilage by microorganisms, in particular food spoilage yeast, has been reported in different food matrices. Zygosaccharomyces species, for example, are well known for their spoilage in high sugar content foods. In the battle against food spoilage, natural antimicrobial peptides derived from plants could be a potential new source of food preservatives. The antimicrobial peptide investigated in this study was Snakin-1, derived from potato tubers. A synthetic form of Snakin-1 was synthesised based on the amino acid sequence of its natural peptide. The peptide was characterised for its inhibitory effect against a number of food spoilage yeast. The peptide's minimum inhibitory concentration was generated and its mechanism of action against Zygosaccharomyces bailii was examined. Membrane permeabilisation caused by the presence of the peptide was observed at the highest concentrations applied, and its ability to withstand high salt concentrations, thermal treatment and a range of pH was also investigated. The peptide's safety for human consumption was studied and no adverse effects were found. Finally, the peptide was applied into different beverages commonly spoiled by Zygosaccharomyces bailii in order to demonstrate the potential application of this synthetic plant antimicrobial peptide.

Treatment of Acinetobacter infections

Importance of the field: Acinetobacter baumannii has emerged as a major cause of healthcare-associated infections. It commonly presents resistance to multiple antimicrobial agents, occasionally including carbapenems and polymyxins, and hence, it is considered the paradigm of multidrug-resistant (MDR) or pandrug-resistant (PDR) bacterium. MDR A. baumannii is a rapidly emerging pathogen, especially in the intensive care setting, causing infections including bacteremia, pneumonia/ventilator-associated pneumonia (VAP), meningitis, urinary tract infection, central venous catheter-related infection, and wound infection.Areas covered in this review: All potential antimicrobial agents that are available for the treatment of Acinetobacter infections are presented. Emphasis was given to the management of nosocomial infections due to MDR A. baumannii and its close relatives, spp. 3 and 13TU. Areas covered include bloodstream infections, pneumonia or VAP, meningitis, urinary tract infection, skin and soft-tissue or wound infections due to Acinetobacter.What the reader will gain: The antibiotics that are usually effective against A. baumannii infections include carbapenems, polymyxins E and B, sulbactam, piperacillin/tazobactam, tigecycline and aminoglycosides. Carbapenems (imipenem, meropenem, doripenem) are the mainstay of treatment for A. baumannii, though carbapenem-resistant Acinetobacter strains have increasingly been reported worldwide in recent years. However, although well-designed trials of new therapeutic approaches are certainly required, the most important factor necessary to guide clinicians in their choice of empirical or targeted therapy should be knowledge of the susceptibility patterns of strains present in their own geographical area.Take home message: Pooled data suggest that infections caused by A. baumannii, especially those with inappropriate treatment, are associated with considerable attributable mortality. The optimal treatment for A. baumannii nosocomial infections has not been established, especially for MDR strains. Therefore, well-designed clinical studies are necessary to guide clinicians on decisions regarding the best therapeutic approach for patients with MDR A. baumannii infections. In addition, new experimental studies are warranted to evaluate the activity and safety of peptides and other novel antibacterial agents for A. baumannii infections.