Synthesis of -Carbamidomethyl Cysteine and Its Use for Quantification of Cysteinyl Peptides by Targeted Proteomics.

Proteomics has played a central role in the identification of reliable disease biomarkers, which are the basis of precision medicine, a promising approach for tackling recalcitrant diseases such as cancer, that elude conventional treatments. Among proteomic methodologies, targeted proteomics employing stable isotope-labeled (SIL) internal standards is particularly suited for the clinical translation of biomarker information owing to its high throughput and accuracy in the quantitative analysis of patient-derived proteomes. Using SIL internal standards ensures the utmost level of confidence in detection and precision in targeted MS experiments.

Integrated Quantitative Phosphoproteomics and Cell-based Functional Screening Reveals Specific Pathological Cardiac Hypertrophy-related Phosphorylation Sites.

Cardiac hypertrophic signaling cascades resulting in heart failure diseases are mediated by protein phosphorylation. Recent developments in mass spectrometry-based phosphoproteomics have led to the identification of thousands of differentially phosphorylated proteins and their phosphorylation sites. However, functional studies of these differentially phosphorylated proteins have not been conducted in a large-scale or high-throughput manner due to a lack of methods capable of revealing the functional relevance of each phosphorylation site.

Comparative proteomic analysis of mouse models of pathological and physiological cardiac hypertrophy, with selection of biomarkers of pathological hypertrophy by integrative Proteogenomics.

To determine fundamental characteristics of pathological cardiac hypertrophy, protein expression profiles in two widely accepted models of cardiac hypertrophy (swimming-trained mouse for physiological hypertrophy and pressure-overload-induced mouse for pathological hypertrophy) were compared using a label-free quantitative proteomics approach. Among 3955 proteins (19,235 peptides, false-discovery rate < 0.01) identified in these models, 486 were differentially expressed with a log fold difference ≥ 0.

Coupling of ryanodine receptor 2 and voltage-dependent anion channel 2 is essential for Ca²+ transfer from the sarcoplasmic reticulum to the mitochondria in the heart.

The structural proximity and functional coupling between the SR (sarcoplasmic reticulum) and mitochondria have been suggested to occur in the heart. However, the molecular architecture involved in the SR-mitochondrial coupling remains unclear. In the present study, we performed various genetic and Ca2+-probing studies to resolve the proteins involved in the coupling process.