Synthesis of Imidazole-Based Molecules under Ultrasonic Irradiation Approaches.

Imidazole-based compounds are a series of heterocyclic compounds that exhibit a wide range of biological and pharmaceutical activities. However, those extant syntheses using conventional protocols can be time-costly, require harsh conditions, and result in low yields. As a novel and green technique, sonochemistry has emerged as a promising method for organic synthesis with several advantages over conventional methods, including enhancing reaction rates, improving yields, and reducing the use of hazardous solvents. Contemporarily, a growing body of ultrasound-assisted reactions have been applied in the preparation of imidazole derivatives, which demonstrated greater benefits and provided a new strategy. Herein, we introduce the brief history of sonochemistry and focus on the discussion of the multifarious approaches for the synthesis of imidazole-based compounds under ultrasonic irradiation and its advantages in comparison with conventional protocols, including typical name-reactions and various sorts of catalysts in those reactions.

Optimizing ABA-based chemically induced proximity for enhanced intracellular transcriptional activation and modification response to ABA.

Abscisic acid (ABA)-based chemically induced proximity (CIP) is primarily mediated by the interaction of the ABA receptor pyrabactin resistance 1-like 1 (PYL1) and the 2C-type protein phosphatase ABI1, which confers ABA-induced proximity to their fusion proteins, and offers precise temporal control of a wide array of biological processes. However, broad application of ABA-based CIP has been limited by ABA response intensity. In this study, we demonstrated that ABA-induced interaction between another ABA receptor pyrabactin resistance 1 (PYR1) and ABI1 exhibited higher ABA response intensity than that between PYL1 and ABI1 in HEK293T cells. We engineered PYR1-ABI1 and PYL1-ABI1 into ABA-induced transcriptional activation tools in mammalian cells by integration with CRISPR/dCas9 and found that the tool based on PYR1-ABI1 demonstrated better ABA response intensity than that based on PYL1-ABI1 for both exogenous and endogenous genes in mammalian cells. We further achieved ABA-induced RNA m6A modification installation and erasure by combining ABA-induced PYR1-ABI1 interaction with CRISPR/dCas13, successfully inhibiting tumor cell proliferation. We subsequently improved the interaction of PYR1-ABI1 through phage-assisted continuous evolution (PACE), successfully generating a PYR1 mutant (PYR1m) whose interaction with ABI1 exhibited a higher ABA response intensity than that of the wild-type. In addition, we tested the transcriptional activation tool based on PYRm-ABI1 and found that it also showed a higher ABA response intensity than that of the wild type. These results demonstrate that we have developed a novel ABA-based CIP and further improved upon it using PACE, providing a new approach for the modification of other CIP systems.