Adipocyte-derived extracellular vesicles increase insulin secretion through transport of insulinotropic protein cargo.

Adipocyte-derived extracellular vesicles (AdEVs) are membranous nanoparticles that convey communication from adipose tissue to other organs. Here, to delineate their role as messengers with glucoregulatory nature, we paired fluorescence AdEV-tracing and SILAC-labeling with (phospho)proteomics, and revealed that AdEVs transfer functional insulinotropic protein cargo into pancreatic β-cells. Upon transfer, AdEV proteins were subjects for phosphorylation, augmented insulinotropic GPCR/cAMP/PKA signaling by increasing total protein abundances and phosphosite dynamics, and ultimately enhanced 1st-phase glucose-stimulated insulin secretion (GSIS) in murine islets.

Internal Peptide Late-Stage Diversification: Peptide-Isosteric Triazoles for Primary and Secondary C(sp )-H Activation.

Secondary C(sp )-H arylations were accomplished by palladium catalysis with triazoles as peptide bond isosteres. The unique power of this approach is highlighted by the possibility of achieving secondary C(sp )-H functionalizations on terminal peptides as well as the unprecedented positional-selective C(sp )-H functionalization of internal peptide positions, setting the stage for modular peptide late-stage diversification.

C-H arylations of 1,2,3-triazoles by reusable heterogeneous palladium catalysts in biomass-derived γ-valerolactone.

C-H arylations were accomplished with a user-friendly heterogeneous palladium catalyst in the biomass-derived γ-valerolactone (GVL) as an environmentally-benign reaction medium. The user-friendly protocol was characterized by ample substrate scope and high functional group tolerance in the C-H arylation of 1,2,3-triazoles, and the palladium catalyst could be recycled and reused in the C-H activation process.

Late-Stage Peptide Diversification by Bioorthogonal Catalytic C-H Arylation at 23 °C in H2 O.

The step-economical late-stage diversification of tryptophan-containing peptides was accomplished through chemo- and site-selective palladium-catalyzed C-H arylation under exceedingly mild reaction conditions. Thus, the C-H functionalization occurred efficiently at 23 °C with a catalyst loading as low as 0.5 mol %, and/or in H2 O.

Late-stage diversification of peptides by metal-free C-H arylation.

The bioorthogonal late-stage diversification of functionalized oligopeptides was accomplished through a metal-free, site-selective C-H arylation of engineered indole derivatives under mild reaction conditions.