Toward the Establishment of a Harmonized Physicochemical Profiling Platform for Therapeutic Oligonucleotides: A Case Study for Aptamers Where the Higher-Order Structure Influences Physical Properties.

Oligonucleotides are short nucleic acids that serve as one of the most promising classes of drug modality. However, attempts to establish a physicochemical evaluation platform of oligonucleotides for acquiring a comprehensive view of their properties have been limited. As the chemical stability and the efficacy as well as the solution properties at a high concentration should be related to their higher-order structure and intra-/intermolecular interactions, their detailed understanding enables effective formulation development. Here, the higher-order structure and the thermodynamic stability of the thrombin-binding aptamer (TBA) and four modified TBAs, which have similar sequences but were expected to have different higher-order structures, were evaluated using ultraviolet spectroscopy (UV), circular dichroism (CD), differential scanning calorimetry (DSC), and nuclear magnetic resonance (NMR). Then, the relationship between the higher-order structure and the solution properties including solubility, viscosity, and stability was investigated. The impact of the higher-order structure on the antithrombin activity was also confirmed. The higher-order structure and intra-/intermolecular interactions of the oligonucleotides were affected by types of buffers because of different potassium concentrations, which are crucial for the formation of the G-quadruplex structure. Consequently, solution properties, such as solubility and viscosity, chemical stability, and antithrombin activity, were also influenced. Each instrumental analysis had a complemental role in investigating the higher-order structure of TBA and modified TBAs. The utility of each physicochemical characterization method during the preclinical developmental stages is also discussed.

Solar-Driven Generation of Hydrogen Peroxide on Phenol-Resorcinol-Formaldehyde Resin Photocatalysts.

Photocatalytic generation of H2O2 from water and O2 under sunlight is a promising artificial photosynthesis reaction to generate renewable fuel. We previously found that resorcinol-formaldehyde resin powders prepared with a high-temperature hydrothermal method become semiconductors comprising π-conjugated/π-stacked benzenoid-quinoid donor-acceptor resorcinol units and are active for photocatalytic H2O2 generation. Here, we have prepared phenol-resorcinol-formaldehyde resins with small amounts of phenol (∼5 mol % relative to resorcinol), which show enhanced photocatalytic activity. Incorporating phenol bearing a single -OH group in the resin matrices relaxes the restriction on the arrangement of the aromatic rings originating from the H-bonding interactions between the resorcinol -OH groups. This creates stronger donor-acceptor π-stacking and increases the electron conductivity of the resins. We have demonstrated that simulated sunlight illumination of the resins in water under an atmospheric pressure of O2 stably generated H2O2 with more than 0.9% solar-to-chemical conversion efficiency.

Triterpenes and flavonol glucuronides from Oenothera cheiranthifolia.

A new ursane-type triterpene, named as cheiranthic acid (1), was isolated from the MeOH extract of whole plants of Oenothera cheiranthifolia (Onagraceae) along with an isomeric pair of known oleanane- and ursane-type triterpenes (arjunolic acid and asiatic acid) and three flavonol glucuronide analogues (quercetin 3-O-glucuronide, its n-butyl ester, and myricetin 3-O-glucuronide). Their structures were elucidated based on spectroscopic evidence.