Dynamic Light Scattering Analysis of Lipid Nanoparticles: Effect of Salts on the Diffusion Interaction Parameter and Hydrodynamic Radius at Infinite Dilution.

The rise in the popularity of lipid nanoparticle (LNP)-based formulations necessitates the need for screening tools to quickly predict their colloidal stability in the presence of common excipients. Protein chemists have employed the diffusion interaction parameter () determined using dynamic light scattering as an indicator of formulation stability, yet this approach has not been applied to particulate systems. Herein, measurements of LNPs revealed behavior dissimilar to that of proteins.

Complexity associated with caprylate binding to bovine serum albumin: Dimerization, allostery, and variance between the change in free energy and enthalpy of binding.

Isothermal titration calorimetry (ITC), differential scanning calorimetry (DSC), and pressure perturbation calorimetry (PPC) were used to study different aspects of the diverse interaction between the fatty acid caprylate and bovine serum albumin (BSA). The ITC thermogram was consistent with exothermic binding to a single site on BSA, which was electrostatic but had little or no hydrophobic contribution. ITC revealed that small changes to solution conditions and temperature were associated with apparent enthalpy-entropy compensation, causing large changes in enthalpy (ΔH) during binding, but with little corresponding changes in free energy (ΔG).

Hypoxia-Responsive Prodrug of ATR Inhibitor, AZD6738, Selectively Eradicates Treatment-Resistant Cancer Cells.

Targeted therapy remains the future of anti-cancer drug development, owing to the lack of specificity of current treatments which lead to damage in healthy normal tissues. ATR inhibitors have in recent times demonstrated promising clinical potential, and are currently being evaluated in the clinic. However, despite the considerable optimism for clinical success of these inhibitors, reports of associated normal tissues toxicities remain a concern and can compromise their utility.

The DNA repair kinase ATM regulates CD13 expression and cell migration.

Classically, ATM is known for its role in sensing double-strand DNA breaks, and subsequently signaling for their repair. Non-canonical roles of ATM include transcriptional silencing, ferroptosis, autophagy and angiogenesis. Angiogenesis mediated by ATM signaling has been shown to be VEGF-independent via p38 signaling.

Dess-Martin periodinane-mediated oxidation of the primary alcohol of cytidine into a carboxylic acid.

Herein the first example of conversion of alcohols into carboxylic acids by use of the Dess-Martin Periodinane (DMP), which is otherwise routinely employed for the conversion to aldehydes, is reported. This methodology will have significant potential utility in the synthesis of cytidine analogues and other related biologically important molecules.