Lipid-based nanoparticles (LBNPs) are an important tool for the delivery of a diverse set of drug cargoes, including small molecules, oligonucleotides, and proteins and peptides. Despite their development over the past several decades, this technology is still hindered by issues with the manufacturing processes leading to high polydispersity, batch-to-batch and operator-dependent variability, and limits to the production volumes. To overcome these issues, the use of microfluidic techniques in the production of LBNPs has sharply increased over the past two years.
View Article and Find Full Text PDFThis review provides an overview of the properties of cyclotides and their potential for developing novel peptide-based therapeutics. The selective disruption of protein-protein interactions remains challenging, as the interacting surfaces are relatively large and flat. However, highly constrained polypeptide-based molecular frameworks with cell-permeability properties, such as the cyclotide scaffold, have shown great promise for targeting those biomolecular interactions.
View Article and Find Full Text PDFClassical 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.
View Article and Find Full Text PDFHydrogen peroxide is the preeminent chemical weapon that organisms use for combat. Individual cells rely on conserved defenses to prevent and repair peroxide-induced damage, but whether similar defenses might be coordinated across cells in animals remains poorly understood. Here, we identify a neuronal circuit in the nematode that processes information perceived by two sensory neurons to control the induction of hydrogen peroxide defenses in the organism.
View Article and Find Full Text PDFLettuce (Lactuca sativa) seeds exhibit thermoinhibition, or failure to complete germination when imbibed at warm temperatures. Chemical mutagenesis was employed to develop lettuce lines that exhibit germination thermotolerance. Two independent thermotolerant lettuce seed mutant lines, TG01 and TG10, were generated through ethyl methanesulfonate mutagenesis.
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