Late-stage peptide labeling with near-infrared fluorogenic nitrobenzodiazoles by manganese-catalyzed C-H activation.

Late-stage diversification of structurally complex amino acids and peptides provides tremendous potential for drug discovery and molecular imaging. Specifically, labeling peptides with fluorescent tags is one of the most important methods for visualizing their mode of operation. Despite major recent advances in the field, direct molecular peptide labeling by C-H activation is largely limited to dyes with relatively short emission wavelengths, leading to high background signals and poor signal-to-noise ratios. In sharp contrast, here we report on the fluorescent labeling of peptides catalyzed by non-toxic manganese(i) via C(sp2)-H alkenylation in chemo- and site-selective manners, providing modular access to novel near-infrared (NIR) nitrobenzodiazole-based peptide fluorogenic probes.

Modelling Metabolic Shifts during Cardiomyocyte Differentiation, Iron Deficiency and Transferrin Rescue Using Human Pluripotent Stem Cells.

Cardiomyocytes rely on specialised metabolism to meet the high energy demand of the heart. During heart development, metabolism matures and shifts from the predominant utilisation of glycolysis and glutamine oxidation towards lactate and fatty acid oxidation. Iron deficiency (ID) leads to cellular metabolism perturbations. However, the exact alterations in substrate metabolism during ID are poorly defined. Using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM), the present study investigated changes in major metabolic substrate utilisation in the context of ID or upon transferrin rescue. Typically, during hiPSC-CM differentiation, the greatest increase in total metabolic output and rate was seen in fatty acid metabolism. When ID was induced, hiPSC-CMs displayed increased reliance on glycolytic metabolism, and six TCA cycle, five amino acid, and four fatty acid substrates were significantly impaired. Transferrin rescue was able to improve TCA cycle substrate metabolism, but the amino acid and fatty acid metabolism remained perturbed. Replenishing iron stores partially reverses the adverse metabolic changes that occur during ID. Understanding the changes in metabolic substrate utilisation and their modification may provide potential for discovery of new biomarkers and therapeutic targets in cardiovascular diseases.