Due to their constrained conformations, cyclic β-amino acids (cβAA) are key building blocks that can fold peptides into compact and rigid structures, improving peptidase resistance and binding affinity to target proteins, due to their constrained conformations. Although the translation efficiency of cβAAs is generally low, our engineered tRNA, referred to as tRNA, enabled efficient incorporation of cβAAs into peptide libraries using the flexible in vitro translation (FIT) system. Here we report on the design and application of a macrocyclic peptide library incorporating 3 kinds of cβAAs: (1,2)-2-aminocyclopentane carboxylic acid (β), (1,2)-2-aminocyclohexane carboxylic acid (β), and (1,2)-2-aminocyclopentane carboxylic acid. This library was applied to an in vitro selection against the SARS-CoV-2 main protease (M). The resultant peptides, BM3 and BM7, bearing one β and two β, exhibited potent inhibitory activities with IC values of 40 and 20 nM, respectively. BM3 and BM7 also showed remarkable serum stability with half-lives of 48 and >168 h, respectively. Notably, BM3A and BM7A, wherein the cβAAs were substituted with alanine, lost their inhibitory activities against M and displayed substantially shorter serum half-lives. This observation underscores the significant contribution of cβAA to the activity and stability of peptides. Overall, our results highlight the potential of cβAA in generating potent and highly stable macrocyclic peptides with drug-like properties.

Ultrasound has attracted much attention in recent years as an external stimulus capable of activating different types of nanomaterials for therapeutic application. One of the characteristics that makes ultrasound an especially appealing triggering stimulus for nanomedicine is its capacity to be non-invasively applied in a focused manner at deep regions of the body. Combining ultrasound with nanoparticles, different biological effects can be achieved. In this work, an overview of the four main types of inducible responses will be provided: inducing drug release, producing ultrasound-derived biological effects, modifying nanoparticle biodistribution and developing theranostic agents. Several examples of each one of these applications are presented here to illustrate the key concepts underlying recent developments in the discipline.

Herein, we describe the preparation of 1-tetralones bearing a remote quaternary stereocenter in a highly enantioselective manner. A sequence of Pd-catalyzed asymmetric 1,4-addition and Rh-catalyzed enantiospecific C-C/C-H activation delivers diverse 1-tetralones with a C4 quaternary stereocenter, which are prepared in good overall yields and high enantioselectivity.

Instructed-assembly (iAssembly or iA) refers to the formation of ordered superstructures of molecules as the consequence of at least one trigger event (e.g., a reaction or a ligand-receptor interaction). As a biomimetic process that transforms from an equilibrium to another equilibrium, iA has emerging as a powerful approach to provide spatiotemporal control for a range of potential biomedical applications, including molecular imaging, cancer therapy, and tissue engineering. This account introduces the general concept of iA in the context of cells and illustrates how to achieve iA for applications. By mainly describing the representative examples of iA and its applications in complex environment, such as cells or animals, and providing the perspectives of the future development of iA, we intend to show that, as a process that bridges self-assembly and self-organization, iA offers chemists a facile mean to explore the emergent properties of molecular assemblies and the dynamics of molecular processes to control cell fate. Particularly, iA promises many wonderful surprises and useful applications in physical and/or life sciences when multiple processes (e.g., self-assembly, instructed-assembly, and self-organization) are taking place simultaneously.