Karayavuz B et al. · Jul 1, 2026
Chirality is of great importance in drug development since both biological targets in the organism and the majority of pharmacologically active compounds created today are chiral. The synthesis and resolution of chiral compounds are critical steps while developing chiral drugs, as the chirality of a molecule can significantly affect its efficacy, safety (side effects and toxicity), and metabolism. While one enantiomer has therapeutic properties, the other enantiomer might be harmful, toxic, or ineffective. In recent years, the trends towards developing single enantiomer drugs have increased in the pharmaceutical industry. Various synthetic strategies and racemic resolution techniques are employed to obtain optically pure chiral drugs. Regulatory authorities also give more priority to assessing the biological efficacy of each chiral drug's enantiomer. This review summarizes the asymmetric synthesis and racemic resolution methods for producing pure enantiomeric pharmaceutical active ingredients and their synthetic intermediates, with examples from the pharmaceutical industry. By examining current approaches and challenges in the field, we aim to provide a comprehensive understanding of the processes that ensure the production of safe and effective chiral-specific drugs.
Chemistry
Sharma L et al. · Jul 1, 2026
Maintaining mitochondrial integrity and function is fundamental to cellular homeostasis. Cells rely on coordinated protein quality control (QC) systems-including intricate chaperone-protease networks, the ubiquitin-proteasome system, and cytosolic surveillance pathways-that together form a dynamic, cell-wide mitostasis network governing the import, folding, synthesis, and degradation of mitochondrial proteins. Disruption of mitochondrial homeostasis, for example, by impairing mitochondrial protein import, induces proteotoxic stress and contributes to human disease. Mass spectrometry (MS)-based proteomics has established itself as an indispensable method to dissect mitostasis at unprecedented depth by enabling systematic quantitative analysis of protein abundance, localization, interactions, stability, and dynamics. In this review, we highlight state-of-the-art MS technologies and multifaceted proteomics approaches used to study mitostasis on a proteome-wide level. These functional analysis approaches build on quantitative MS methods employing label-free, metabolic, and chemical labeling strategies, which allow precise tracking of proteome dynamics in response to different cellular conditions including stress. Spatial and interaction-based approaches, such as affinity purification-MS, proximity labeling, and complexome profiling, provide detailed insight into the organization and regulation of the complex mitochondrial organizing system, chaperone networks, and protein QC pathways. Furthermore, we discuss advanced methodologies such as nascent chain and dynamic proteomics strategies, which offer a proteome-wide comprehension of early stress responses and fast regulation. The skillful integration of temporal, spatial subcellular, interaction, nascent, and dynamic proteomics approaches now enables a systems-level assessment of mitostasis, paving the way for a holistic while nuanced understanding of this essential cellular process and the underlying molecular mechanisms.
Chemistry
Zhang A et al. · Jul 1, 2026
In light of the centennial of the Schrödinger equation, this article addresses the popular idea that quantum mechanical effects play an important role in biological systems. We start by defining what is qualified as a quantum effect. We then clarify the idea that quantum mechanical tunneling is a crucial factor in enzyme catalysis. Here we show that quantum tunneling is in fact anticatalytic and that there is no consistent theoretical and experimental evidence that the tunneling effects are enhanced significantly by enzymes relative to the corresponding reference solution reactions. We next turn to electron transfer reactions, arguing that in most cases the efficiency of the reaction is controlled by classical effects. We also consider the low barrier hydrogen bond idea and clarify its anticatalytic nature. In addition, we present a specific case study of electron transfer in a protein system potentially responsible for bird navigation, providing a concrete example for evaluating the role of quantum and classical effects under biologically relevant conditions. We argue that for the electron transfer step in this system, the most important control is associated with the classical control of the relevant potential surfaces and the fluctuations of the key energy gaps.
Chemistry
Shearer JJ et al. · Jun 23, 2026
Background Heart failure (HF) is a complex syndrome with high mortality. Proteomics risk scores have shown promise in predicting mortality beyond guideline-recommended clinical tools. It is crucial to understand how risk scores generated by different methods and populations perform, and whether they highlight the same protein targets relevant to outcomes. Methods To examine whether the study design impacts proteomics scores designed to predict mortality in HF, we evaluated three published risk scores that used the SomaScan assay to measure plasma proteins in a community cohort, clinical trial, and registry. Each score was assessed in the aforementioned community cohort and Cox models examined the association of a 1-standard deviation increase in score with mortality, with and without adjustment for clinical covariates. Performance of each risk score to predict 5-year mortality risk was assessed using calibration plots and time-dependent area under the curve and compared with a clinical model. Results Risk scores were similarly distributed and moderately correlated (Pearson correlation coefficient = 0.59-0.76). A 1-standard deviation increase in each risk score was associated with an increased risk of all-cause mortality: community cohort (HR = 2.70, 95% CI: 2.50-2.91); clinical trial (HR = 1.76, 95% CI: 1.65-1.88); registry (HR = 1.70, 95% CI: 1.6-1.81). Risk remained after adjustment for clinical covariates, although slightly attenuated, and similar across different ejection fraction categories. All risk scores showed strong calibration across the risk levels, alone, with an average expected over observed ratio ranging between 0.96-1.56. Seven proteins were included in at least two risk scores, with renin being included in all three. Conclusions All three proteomics risk scores improved risk stratification in HF patients beyond guideline recommended clinical tools, independent of study design and ejection fraction. These results demonstrate that proteomics risk scores can enhance risk stratification across the HF syndrome, even when derived from different methods and populations.
Chemistry