A Hitchhiker's Guide to Problem Selection in Carbohydrate Synthesis.

Oligosaccharides are ubiquitous in molecular biology and are used for functions ranging from governing protein folding to intercellular communication. Perhaps paradoxically, the exact role of the glycan in most of these settings is not well understood. One reason for this contradiction concerns the fact that carbohydrates often appear in heterogeneous form in nature. These mixtures complicate the isolation of pure material and characterization of structure-activity relationships. As a result, a major bottleneck in glycoscience research is the synthesis and modification of pure materials. While synthetic and chemoenzymatic methods have enabled access to homogeneous tool compounds, a central problem, particularly for newer synthetic chemists, is the matter of problem selection. This outlook aims to provide an entry level overview of fundamental principles in carbohydrate chemistry with an eye toward enabling solutions to frontier challenges.

Insight into Cellular Uptake and Transcytosis of Peptide Nanoparticles in Spodoptera frugiperda Cells and Isolated Midgut.

Silencing genes in insects by introducing double-stranded RNA (dsRNA) in the diet holds promise as a new pest management method. It has been demonstrated that nanoparticles (NPs) can potentiate dsRNA silencing effects by promoting cellular internalization and protecting dsRNA against early degradation. However, many mysteries of how NPs and dsRNA are internalized by gut epithelial cells and, subsequently, transported across the midgut epithelium remain to be unraveled. The sole purpose of the current study is to investigate the role of endocytosis and transcytosis in the transport of branched amphipathic peptide nanocapsules (BAPCs) associated with dsRNA through midgut epithelium cells. Spodoptera frugiperda midguts and the epithelial cell line Sf9, derived from S. frugiperda, were used to study transcytosis and endocytosis, respectively. Results suggest that clathrin-mediated endocytosis and macropinocytosis are largely responsible for cellular uptake, and once within the midgut, transcytosis is involved in shuttling BAPCs-dsRNA from the lumen to the hemolymph. In addition, BAPCs were not found to be toxic to Sf9 cells or generate damaging reactive species once internalized.

Metal-Free Selective Modification of Secondary Amides: Application in Late-Stage Diversification of Peptides.

Here we solve a long-standing challenge of the site-selective modification of secondary amides and present a simple two-step, metal-free approach to selectively modify a particular secondary amide in molecules containing multiple primary and secondary amides. Density functional theory (DFT) provides insight into the activation of C-N bonds. This study encompasses distinct chemical advances for late-stage modification of peptides thus harnessing the amides for the incorporation of various functional groups into natural and synthetic molecules.

Selective Triazenation Reaction (STaR) of Secondary Amines for Tagging Monomethyl Lysine Post-Translational Modifications.

Lysine monomethylation (Kme) is an impactful post-translational modification (PTM) responsible for regulating biological processes and implicated in diseases, thus there is great interest in identifying these methylation marks globally. However, the progress in this area has been challenging because the addition of a small methyl group on lysine leads to negligible change in the bulk, charge, and hydrophobicity. Herein, we report an empowering chemical technology selective triazenation reaction, which we term "STaR", of secondary amines using arene diazonium salts to achieve highly selective, rapid, and robust tagging of Kme peptides from a complex mixture under biocompatible conditions. Although the resulting triazene-linkage with Kme is stable, we highlight the efficient decoupling of the triazene-conjugate to afford unmodified starting components under mild conditions when desired. Our work establishes a unique chemoselective, traceless bioconjugation strategy for the selective enrichment of Kme PTMs.