Macromolecules最新文献

The genetic code is the foundation for all life. With few exceptions, the translation of nucleic acid messages into proteins follows conserved rules, which are defined by codons that specify each of the 20 proteinogenic amino acids. For decades, leading research groups have developed a catalogue of innovative approaches to extend nature’s amino acid repertoire to include one or more noncanonical building blocks in a single protein. In this review, we summarize advances in the history of in vitro and in vivo genetic code expansion, and highlight recent innovations that increase the scope of biochemically accessible monomers and codons. We further summarize state-of-the-art knowledge in engineered cellular translation, as well as alterations to regulatory mechanisms that improve overall genetic code expansion. Finally, we distill existing limitations of these technologies into must-have improvements for the next generation of technologies, and speculate on future strategies that may be capable of overcoming current gaps in knowledge.

Technological advances and breakthrough developments in the pharmaceutical field are knocking at the door of the “undruggable” fortress with increasing insistence. Notably, the 21st century has seen the emergence of macrocyclic compounds, among which cyclic peptides are of particular interest. This new class of potential drug candidates occupies the vast chemical space between classic small-molecule drugs and larger protein-based therapeutics, such as antibodies. As research advances toward clinical targets that have long been considered inaccessible, macrocyclic peptides are well-suited to tackle these challenges in a post-rule of 5 pharmaceutical landscape. Facilitating their discovery is an arsenal of high-throughput screening methods that exploit massive randomized libraries of genetically encoded compounds. These techniques benefit from the incorporation of non-natural moieties, such as non- proteinogenic amino acids or stabilizing hydrocarbon staples. Exploiting these features for the strategic architectural design of macrocyclic peptides has the potential to tackle challenging targets such as protein–protein interactions, which have long resisted research efforts. This Review summarizes the basic principles and recent developments of the main high-throughput techniques for the discovery of macrocyclic peptides and focuses on their specific deployment for targeting undruggable space. A particular focus is placed on the development of new design guidelines and principles for the cyclization and structural stabilization of cyclic peptides and the resulting success stories achieved against well-known inaccessible drug targets.

This work, which overviews defect chemistry of TiO₂ (rutile), is focused on atomic-size structural defects that are thermodynamically reversible. Here it is shown that thermodynamics can be used in defect engineering of TiO₂-based energy materials, such as photoelectrodes and photocatalysts. We show that surface segregation of defects leads to the building-up of new surface structures that are responsible for reactivity. Since rational design of surface properties requires in situ surface characterization in operational conditions, expansion of bulk defect chemistry to surface defect chemistry requires a defect-related surface-sensitive tool for in situ monitoring of defect-related properties at elevated temperatures corresponding to defect equilibria and in a controlled gas-phase environment. Here we show that the high-temperature electron probe is a defect-related surface-sensitive tool that is uniquely positioned to aid surface defect engineering and determine unequivocal surface properties. The related applied aspects are considered for photoelectrochemical water splitting and the performance of solid oxide fuel cells. Here we report that trail-blazing studies on in situ surface monitoring of TiO₂ during gas/solid equilibration, along with in situ characterization of surface semiconducting properties, leads to the discovery of a segregation-induced low-dimensional surface structure that is responsible for stable performance of oxide semiconductors, such as TiO₂, in operational conditions.

The copolymerization of CO₂ and epoxides presents a transformative approach to converting greenhouse gases into aliphatic polycarbonates (CO₂-PCs), thereby reducing the polymer industry’s dependence on fossil resources. Over the past 50 years, a wide array of metallic catalysts, both heterogeneous and homogeneous, have been developed to achieve precise control over polymer selectivity, sequence, regio-, and stereoselectivity. This review details the evolution of metal-based catalysts, with a particular focus on the emergence of organoborane catalysts, and explores how these catalysts effectively address kinetic and thermodynamic challenges in CO₂/epoxides copoly₂merization. Advances in the synthesis of CO₂-PCs with varied sequence and chain architectures through diverse polymerization protocols are examined, alongside the applications of functional CO₂-PCs produced by incorporating different epoxides. The review also underscores the contributions of computational techniques to our understanding of copolymerization mechanisms and highlights recent advances in the closed-loop chemical recycling of CO₂-sourced polycarbonates. Finally, the industrialization efforts of CO₂-PCs are discussed, offering readers a comprehensive understanding of the evolution and future potential of epoxide copolymerization with CO₂.