Systematic mutagenesis of Polerovirus protein P0 reveals distinct and overlapping amino acid functions in Nicotiana glutinosa.

The protein P0 serves as the viral suppressor of RNA silencing (VSR) for poleroviruses, but elicits the hypersensitive response (HR) in specific Nicotiana species. We subjected P0 proteins from turnip yellows virus (P0) and potato leafroll virus (P0) to serial deletion and performed extensive site-directed mutagenesis of P0. Most deletions of the N-terminus and many substitution mutations disrupted both HR elicitation and VSR activity.

Chemical Synthesis of a Potent Antimicrobial Peptide Murepavadin Using a Tandem Native Chemical Ligation/Desulfurization Reaction.

Classical approaches for the backbone cyclization of polypeptides require conditions that may compromise the chirality of the C-terminal residue during the activation step of the cyclization reaction. Here, we describe an efficient epimerization-free approach for the Fmoc-based synthesis of murepavadin using intramolecular native chemical ligation in combination with a concomitant desulfurization reaction. Using this approach, bioactive murepavadin was produced in a good yield in two steps.

Anti-Inflammatory Effects of RTD-1 in a Murine Model of Chronic Lung Infection: Inhibition of NF-κB, Inflammasome Gene Expression, and Pro-IL-1β Biosynthesis.

Vicious cycles of chronic airway obstruction, lung infections with , and neutrophil-dominated inflammation contribute to morbidity and mortality in cystic fibrosis (CF) patients. Rhesus theta defensin-1 (RTD-1) is an antimicrobial macrocyclic peptide with immunomodulatory properties. Our objective was to investigate the anti-inflammatory effect of RTD-1 in a murine model of chronic lung infection.

Engineered Cyclotides with Potent Broad in Vitro and in Vivo Antimicrobial Activity.

The search for novel antimicrobial agents to combat microbial pathogens is intensifying in response to the rapid development of drug resistance to current antibiotic therapeutics. Respiratory failure and septicemia are the leading causes of mortality among hospitalized patients. Here, the development of a novel engineered cyclotide with effective broad-spectrum antibacterial activity against several ESKAPE bacterial strains and clinical isolates is reported.