ChemBioChem最新文献

Several RF-DNA conjugates are synthesized, and the relationship between the uptake efficiency and the physicochemical properties is systematically investigated. RF-DNA conjugates carrying two C8F17 groups at the terminus of a DNA strand form a nano-assembly with the highest DNA content, leading to the greatest cellular uptake via scavenger receptors. More details can be found in article 10.1002/cbic.202400436 by Ai Kohata, Kohsuke Aikawa, and co-workers.

Original covalent probes with an N-acyl-N-alkyl sulfonamide cleavable linker were developed to target a broad set of human Matrix Metalloproteases (MMPs). The electrophilicity of this cleavable linker was modulated to improve the selectivity of the probes as well as reduce their unspecific reactivity in complex biological matrices. We first demonstrated that targeting the S₃ subsite of MMPs enables access to broad-spectrum affinity-based probes that exclusively react with the active version of these proteases. The probes were further assessed in proteomes of varying complexity, where human MMP-13 was artificially introduced at known concentration and the resulting labeled MMP was imaged by in-gel fluorescence imaging. We showed that the less reactive probe was still able to covalently modify MMP-13 while exhibiting reduced off-target unspecific reactivity. This study clearly demonstrated the importance of finely controlling the reactivity of the NASA warhead to improve the selectivity of covalent probes in complex biological systems.

Biofilms, which are resistant to conventional antimicrobial treatments, pose significant challenges in medical and industrial environments. This study introduces manganese complex-gold nanoparticles (Mn-DPA-AuNPs) as a hybrid strategy for biofilm inhibition and eradication. Upon exposure to green light, these nanoparticles significantly enhance the generation of reactive oxygen species (ROS), including hydrogen peroxide and superoxide. This activity substantially reduces the regrowth potential of the surviving bacteria within the biofilm, with marked efficacy noted in Pseudomonas aeruginosa PAO1. This study highlights the potential of integrating manganese complexes with gold nanoparticles to develop advanced antimicrobial agents against resistant biofilms, offering a promising approach to enhance microbial control in diverse settings.

This study introduces a novel one-pot enzymatic cascade approach for converting toxicants and continuously generating an electron acceptor for production of sugar acids. This method offers a promising solution to concerns about pesticide toxicity and environmental contamination by transforming hazardous substances into a useful electron acceptor. This acceptor is then utilized to produce valuable chemicals with broad industrial applications, particularly in the food and pharmaceutical sectors. The cascade reaction employs organophosphate hydrolase (OPD) to convert pesticides into 4-nitrophenol (4-NP), which is subsequently transformed into 1,4-benzoquinone by HadA monooxygenase (HadA). 1,4-benzoquinone serves as an electron acceptor in the catalysis of sugar acid formation via pyranose dehydrogenase (PDH). The results indicate that this cascade reaction effectively converts lactose to lactobionic acid and xylose to 2-keto-xylonic acid. The latter can be further processed into xylonic acid through NaBH₄ reduction. Notably, the one-pot reaction yields up to 10 % higher compared to the direct addition of 1,4-benzoquinone. The synthesized xylonic acid exhibits exceptional water uptake properties in hydrogels, and the synthesized lactobionic acid shows antioxidant activity comparable to well-established antioxidants. These findings demonstrate the technological viability of these reaction cascades for various applications.

Nucleic acid conjugation methodologies involve linking the nucleic acid sequence to other (bio)molecules covalently. This typically allows for nucleic acid property enhancement whether it be for therapeutic purposes, biosensing, etc. Here, we report a streamlined, aqueous compatible, on-column conjugation methodology using nucleic acids containing a site-specific amino-modifier. Both monophosphates and carboxylates were amenable to the conjugation strategy, allowing for the introduction of a variety of useful handles including azide, aryl, and hydrophobic groups in DNA. We find that an on-column approach is superior to post-synthetic template-directed synthesis, mainly with respect to product purification and recovery.

Subcellular compartmentalization is a universal feature of all cells. Spatially distinct compartments, be they lipid- or protein-based, enable cells to optimize local reaction environments, store nutrients, and sequester toxic processes. Prokaryotes generally lack intracellular membrane systems and usually rely on protein-based compartments and organelles to regulate and optimize their metabolism. Encapsulins are one of the most diverse and widespread classes of prokaryotic protein compartments. They self-assemble into icosahedral protein shells and are able to specifically internalize dedicated cargo enzymes. This review discusses the structural diversity of encapsulin protein shells, focusing on shell assembly, symmetry, and dynamics. The properties and functions of pores found within encapsulin shells will also be discussed. In addition, fusion and insertion domains embedded within encapsulin shell protomers will be highlighted. Finally, future research directions for basic encapsulin biology, with a focus on the structural understand of encapsulins, are briefly outlined.

This review provides a perspective on the industrial application potential of sugar beet pulp (SBP) derived monosaccharides. The broad application of these monosaccharides could contribute to bio-based alternatives and sustainable practices, essential for the transition towards a more circular economy. This review focuses on the utilization and application of two SBP monosaccharides, d-galacturonic acid (d-GalA) and l-arabinose (l-Ara), derived from pectin and hemicellulose. These polysaccharides are major components of sugar beet pulp, an important side stream of sucrose production. d-GalA and l-Ara are therefore abundant in biomass and offer unique molecular structures amenable to selective chemical or enzymatic modifications. We review their application in various industrial applications such as the development and production of bioactive compounds, home and personal care products, and other industries.

The abnormal aggregation and subsequent deposition of amyloid β-protein (Aβ) in the brain are considered central to the pathogenesis of Alzheimer's disease. The two major species of Aβ are Aβ40 and Aβ42, present at an approximate ratio of 9 : 1. Accumulating evidence suggests that neuronal membranes are an important platform of amyloidogenesis by Aβ. However, information on the aggregational behaviors of coexistent Aβ40 and Aβ42 on membranes is lacking. In this study, the aggregation and resultant cytotoxicity of coexistent Aβ40 and Aβ42 at a physiologically relevant ratio were investigated by fluorescence techniques. We found that the degree of coexistence of both Aβs in aggregates increased as the assembly proceeded, and reached a maximum in fibrils. Cross-seeding experiments supported the hypothesis that Aβ40 and Aβ42 interact with each other in the fibrillar states when formed on membranes. However, the cytotoxicity of the mixed fibrils was weaker than that of Aβ42 fibrils, suggesting the possibility that Aβ40 attenuates the toxicity of Aβ42 by forming mixed fibrils. In contrast, the degree of coexistence was significantly lower in aqueous phase aggregation, highlighting different aggregation mechanisms between in membranes and in the aqueous phase.

The enantioselective reduction of prochiral ketones catalyzed by horse liver alcohol dehydrogenase (HLADH), was investigated via a hybrid computational approach, for molecular reactions involved in chiral synthesis of S-alcohols, when the natural co-factor, 1,4-dihyronicotinamide adenine dinucleotide, 1,4-NADH, was replaced with biomimetic co-factor, N-benzyl-1,4-dihydronicotinamide, 1. We surmised that different hydride and proton transfer mechanisms were involved using co-factor, 1. An alternative mechanism, where the hydride transfer step occurred, via an η¹-keto-S-η²-5,6-1,4-dihydronicotinamide-Zn(II) complex, was previously investigated with a model of the HLADH-Zn(II) catalytic site (J. Organometal. Chem. 2021, 943, 121810). Presently, we studied canonical and alternative mechanisms compared to models of the entire enzyme structure. We disproved the η²-Zn(II) complex, and discovered a canonical hydride transfer from biomimetic 1,4-NADH, 1, to the Zn(II) bound prochiral ketone substrate, followed by a new proton relay, consisting of a water chain connecting His51 to Ser48 that accomplished the S-alkoxy anion's protonation to yield the final S-alcohol product. The HLADH catalysis, with biomimetic co-factor, 1, that replaced the ribose group, the 5'-diphosphate groups, and the adenine nucleotide with a N-benzyl group, has provided a new paradigm for the design of other structures of 1,4-NADH biomimetic co-factors, including their economic value in biocatalysis reactions.

Guided by molecular networking based on single-molecule stretching assay, an unprecedented pyranonaphthoquinone, methyl kalafunginate (1) and five known compounds 2-6 were isolated from Streptomyces tanashiensis DSM 731. Compound 1 was characterized through a combination of spectroscopic techniques, including 1D and 2D NMR analysis, ECD calculation, and X-ray crystallography. Interestingly, we discovered that compound 1 was spontaneously converted from kalafungin (4) in methanol solution. All isolated compounds, except for compound 3, were assessed for their cytotoxic potential against a panel of five human cancer cell lines: A549, HepG2, BxPC-3, SW620, and C4-2B. Compounds 1, 2, 4, and 5 exhibited remarkable cytotoxicity with IC₅₀ values below 2.382 μM, suggesting their potential as promising anticancer agents. These findings highlight the significance of using a combined approach of single-molecule stretching assays and molecular networking for efficiently discovering novel natural products with potential therapeutic applications.