ChemBioChem最新文献

ThiF-like proteins are members of the widespread E1-like enzyme superfamily. The eponymous ThiF enzyme was first described in thiamin biosynthesis as part of Escherichia coli's primary metabolism, and homologous proteins have been subsequently discovered in secondary metabolism. These ThiF-like enzymes are united in their defining ability to perform nucleotidylation of a carboxyl group to generate an activated, electrophilic intermediate, a feature it shares with the structurally related ubiquitin-activating enzymes. From here, an array of different nucleophiles are used across distinct biosynthetic pathways to yield diverse structural scaffolds. In this review, we discuss various ThiF-like enzymes that perform nucleotidylation to facilitate a diverse array of interesting and rare chemistry on different types of substrates, as well as showcase some of the shared structural features.

The Front Cover depicts a cell surface with a human serotonin transporter protein, illuminated by the spectrum of visible light and surrounded by several photochemical tools. The molecular structures are, from left to right, azo-5HT1, azo-escitalopram, RuBi-5-HT, and SERTlight. Each represents a different group of compounds discussed in the Review Artilce by Michael A. Kienzler and co-workers (DOI: 10.1002/cbic.202500276). The other proteins on the cell surface are various human serotonin receptors.

Natural products are widely used as pharmaceuticals and agrochemicals, or as active ingredients in food and cosmetics. Their biosynthesis typically involves a series of enzyme-controlled reactions in dedicated liquid environments. The reconstruction of these multistep transformations under in vitro conditions bears significant potential for technical utilization. However, the concurrent operation of multiple enzymes in a single reaction flask or reactor is often associated with major challenges. Herein, the difficulties in reaching high substrate conversion and product yields with in vitro enzyme cascades are summarized. Furthermore, both established and emerging concepts for improving their performance are discussed.

Glycosaminoglycans (GAGs) are linear, negatively charged biopolymers that modulate complex biological processes, such as blood coagulation, immune regulation, or viral entry. Their sulfation pattern and chain length govern how strongly they bind to other physiologically relevant species. Most of these interactions rely on electrostatic forces facilitated by the strong polyanionic properties of GAGs; therefore, considering these from a polyelectrolyte vantage point can help understand how such charge-based, often transient interactions contribute to physiological and pathological processes. While the different GAG classes share key electrostatic properties, they exhibit unique structural features that shape their function. Here, it is highlighted on how modern separation and analytical tools exploit the polyanionic character of GAGs to dissect subtle structural details. For these, the fundamental description of their charge–charge interactions is crucial. With this knowledge, modified GAGs, synthetic GAG mimetics, or GAG-binding molecules can be designed that replicate or refine their key properties and show promise for therapeutic and biomedical applications. Altogether, recognizing the importance of GAGs as polyelectrolytes provides vital knowledge on how their charge distribution mediates crucial biomolecular interactions in health and disease, and thus it helps complete our knowledge on fundamentally important biopolymers.

Chemical biology has reshaped the ability to investigate complex biological systems at the molecular level. In this context, chemical reporters have become important tools for labeling and tracking biomolecules in living systems with spatial and temporal precision. In plant biology, they provide an alternative to genetic approaches and allow the study of dynamic processes in species or organs that are not easily accessible. Through the use of click and bioorthogonal chemistry, small-molecule probes can be metabolically incorporated into specific molecular scaffolds such as sugars, monolignols, amino acids, and lipids. These probes make it possible to follow events like glycosylation, lignification, lipid turnover, or protein synthesis in living plant tissues. This review presents an overview of current chemical reporter strategies, from molecular design and synthetic considerations to their application in plant imaging. Herein, how these tools have contributed to the development of plant chemical biology by enabling precise and modular investigations of plant structure and metabolism is described. Herein, it is also examined how chemical reporters have entered interdisciplinary contexts, including collaborations between science and the arts. By converting molecular-level information into visual and sensory formats, these approaches open new perspectives for research, education, and communication across scientific and creative disciplines.

Sugar nucleotides represent the cornerstone building blocks for glycan biosynthesis. While methods to access these crucial biomolecules using traditional batch synthetic chemistry and enzymatic approaches have blossomed, uptake using flow-based synthesis is burgeoning. This perspective analyzes recent advances concerning enzyme immobilization and continuous flow biocatalysis for sugar nucleotide production and usage. Evaluation of related technologies is also discussed, highlighting new enzyme immobilization approaches, novel reactor design, and improved downstream processing as areas that must evolve to enable wider, scalable access to sugar nucleotides as commodity chemicals.

In recent years, chemical modification techniques based on dehydroalanine (Dha) have become a prominent area in the functionalization of peptides and proteins due to their high efficiency and site selectivity. This article reviews the recent advancements in the modification of Dha-containing peptides and proteins. Focusing on the chemical properties of Dha, the advantages of nucleophilic addition reactions, free radical chemistry, metal-catalyzed cross-coupling reactions, and cycloaddition reactions in peptide and protein modification are discussed, as well as their applicability in the development of novel biocompatible methods. Additionally, the article explores the current limitations of these techniques and highlights future challenges that need to be addressed.

Peptide stapling has emerged as a powerful strategy to stabilize α-helical structures in peptides, thereby enhancing their proteolytic resistance, membrane permeability, and biological activity. Among the various stapling methodologies, hydrocarbon stapling via ruthenium-catalyzed ring-closing metathesis remains the most widely adopted due to its robust chemical efficiency and synthetic compatibility with solid-phase peptide synthesis. This review summarizes key advancements in hydrocarbon stapling technologies, including mono- and multiple-stapling, solution- and solid-phase approaches, and newer developments such as stitched and aza-stapled peptides. The integration of rigidified anchoring residues (e.g., cyclobutane or carbocyclic α, α-disubstituted amino acids) and orthogonal metathesis strategies has significantly expanded the structural diversity and functional potential of stapled peptides. Furthermore, novel bioorthogonal modifications and imaging capabilities, such as Raman-active diyne bridges, have opened new directions in therapeutic and diagnostic applications. Together, these innovations underscore the growing utility of stapled peptides in modulating protein–protein interactions and advancing peptide drug discovery.

On May 8–9, 2025, the fifth edition of the NextGenBiocat symposium was held in Milano, Italy. The event has established itself as a key meeting point for the international scientific community engaged in the study of innovative enzymatic processes. The symposium aims to highlight the contributions of the next generation of researchers providing a dynamic and multidisciplinary forum to discuss the latest frontiers in biocatalysis.

DNA's programable thermodynamics, structural versatility, and ease of synthesis makes it an ideal material for constructing molecular devices. While many biological systems are powered by proton gradients to drive dynamic processes, harnessing pH differences in DNA nanotechnology is possible through pH-responsive DNA motifs. Existing strategies, however, often depend on strict sequence constraints or nonphysiological pH conditions, limiting their applicability in complex DNA origami structures. In this article, a nucleoside with pH-sensitive base pairing is developed that reversibly switches its pairing specificity near physiological pH. This unnatural building block is recognized by standard polymerases, and its pairing behavior can be controlled by pH. Characterization of the base pairing properties reveals that duplex stability varies with pH, while canonical sequences remain unaffected. This design enables programable sequence motifs that transition between duplex and single-stranded DNA in response to pH changes. Our unnatural nucleoside therefore provides a versatile tool for dynamic DNA nanotechnology, with potential applications in DNA nanomachines, biosensing, and targeted drug delivery. Additionally, its physiological pK_a may enable general acid–base catalysis in ribozymes or DNAzymes, analogous to histidine in protein enzymes.