Browse Articles

Peptide condensates are known to regulate compartmentalized enzymatic reactions, however, the influence of condensate chemical composition on enzymatic reactions is still poorly understood. Here, the authors study β-galactosidase as a simple enzymatic model and reveal that product formation is enhanced in heterotypic peptide-RNA condensates, but the reaction is restricted in homotypic peptide condensates.

Isofagomine (IFG) and its analogs have promising glycosidase inhibitory activities, however, a flexible synthetic strategy toward C5a-functionalized IFGs remains to be achieved. Here, the authors show a practical synthesis of C5a-S and R-aminomethyl IFG derivatives via diastereoselective addition of cyanide to cyclic nitrone, and the synthesized derivatives are subsequently assessed for their efficacy as GCase stabilizers.

Stereoselective production of trans-4-substituted cyclohexane-1-amines—including a key intermediate in the synthesis of antipsychotic drug cariprazine—remains challenging. Here, the authors develop a process catalyzed by a single transaminase to produce trans-4-substituted cyclohexane-1-amines from the corresponding cis/trans-diastereomeric mixtures via a cis-deamination approach in continuous-flow, to achieve a dynamic cis-to-trans isomerization.

Combinatorial biosynthesis of natural products is a method to synthesize structurally diverse molecules with defined modifications. Here, the authors review the various approaches used for combinatorial biosynthesis of fungal natural products by engineering biosynthetic enzymes and pathways to generate novel molecules.

Fluorescence resonance energy transfer (FRET) is one of the most important fluorescence mechanisms, with multi-step FRET systems enabling sequential energy transfer as seen in natural photosynthetic systems. Here, the authors review recent progress in exploiting discrete supramolecular assemblies to achieve multi-step FRET between donors and multiple acceptors.

Asparaginyl ligases have been utilized as valuable tools for protein engineering, such as through site-specific bioconjugation or surface modification, however, their application is limited due to time-consuming preparation processes and unstable activities. Here, the authors develop a truncated protein ligase OaAEP1-C247A-aa55-351 from an OaAEP1-C247A mutant, which simplifies the preparation steps, tolerates a wider pH range, and enhances the catalytic activities by using efficient recognition and nucleophile motifs.

Transfer learning is known to enhance molecular property prediction in limited data sets, however, negative transfer due to insufficient relatedness between source and target tasks continues to be a major challenge. Here, the authors develop a principal gradient-based measurement to evaluate the quantitative transferability from the source property to the target property before applying transfer learning, significantly improving the transfer learning performance.

Understanding the stability and activity of freeze-dried bio-macromolecules at low degrees of hydration is crucial for pharmaceutical and food industries, however, the building of in silico models for dynamical studies at a molecular level needs careful consideration. Here, the authors propose a modelling protocol that mimics experimental protein lyophilization, and proteins in weakly hydrated amorphous states, and validate it against experimental neutron scattering data.

Identifying molecular properties of compounds that best correlate with outer membrane permeation and growth inhibition could guide the discovery of new antibiotics. Here, the authors evaluate 174 molecular descriptors in 1260 antimicrobial compounds and study their correlations with antibacterial activity in Gram-negative Pseudomonas aeruginosa to derive a statistical protocol to identify mechanistic predictors of outer membrane permeation.

Water at the surface of proteins is known to be critically important in maintaining their conformation and function, but the dynamics of the backbone hydration of peptides remains somewhat elusive. Here, the authors study the hydrogen-bonding structural dynamics of N-ethylpropionamide, a β-peptide model, in heavy water using nonlinear infrared spectroscopy and MD simulations.

Mass spectrometry-based quantitative chemoproteomics is widely used for the identification of protein targets as well as modified residues, however, sample preparation and data analysis remain tedious. Here, the authors develop silane-based cleavable linkers functionalized tandem mass tags as click-compatible isobaric tags, introducing the isobaric label earlier in sample preparation, achieving decreased sample preparation time, with high coverage and high-accuracy quantification.

Understanding the stability of the eye lens protein human gamma-D crystallin (HGD) is essential to developing tools to prevent the formation of cataracts, however, structural investigations of the response of HGD to ultraviolet radiation are lacking. Here, the authors use continuous illumination serial crystallography to directly probe the mechanism of R36S HGD in response to ultraviolet radiation damage.

Dynamic microscale droplets produced by liquid–liquid phase separation (LLPS) have emerged as appealing biomaterials, but their instability hinders their assembly into high-order structures with collective behaviors. Here, the authors review current strategies for stabilizing droplets, as well as recent developments in the applications of such LLPS droplets, and provide insights into how stabilized droplets can self-assemble into higher-order structures that display coordinated functions.

Mass transport at surfaces determines the kinetics of processes such as heterogeneous catalysis and thin-film growth, but our fundamental understanding of the contributions of molecular degrees of freedom to the process remains incomplete. Here, the authors use neutron spectroscopy together with theoretical methods to explain the “rolling” motion of triphenylphosphine adsorbed on exfoliated graphite.

ATP phosphoribosyltransferase is a multi-protein complex where the catalytic protein HisGS is allosterically regulated by the regulatory protein HisZ; however, the protein dynamics of HisGS in enzyme catalysis remain underexplored. Here, the authors investigate the catalytic effect of isotope-labeled HisGS, revealing that the catalytic rate of HisZ-activated HisGS decreases in a mass-dependent fashion at low temperatures, which correlates to product release.

Reduced molecular graphs can integrate higher-level chemical information and leverage advantages from atom-level graph neural networks. Here, the authors introduce the Multiple Molecular Graph eXplainable model, investigating the effects of multiple molecular graphs, including Atom, Pharmacophore, JunctionTree, and FunctionalGroup, on model learning and interpretation from various perspectives

Individual metal atoms and few-atom metal clusters have shown promising catalytic activities, however, their exploitation in the total synthesis of complex organic molecules remains underexplored. Here, the authors develop a total synthesis of the bioactive natural product (±)-Licarin B involving key steps catalyzed by soluble individual Pd atoms and Cu/Pd/Pt clusters, achieving an 11-step linear synthesis and overall yield of 13.1%.

Wheat gluten is a bio-based alternative to fossil-based polymers in thermoplastic and crosslinked foams, and it has been shown that it is possible to extrude foams based on wheat gluten. Here, the authors explore the impact of three naturally occurring additives (genipin, gallic acid, and citric acid) on the mechanical and liquid absorption properties of foam-extruded wheat gluten.

Molecular editing has been used for the late-stage functionalization of chemical scaffolds at the atomic level, however, chemically editing carbohydrates by inserting a foreign glycan remains underexplored. Here, the authors develop a cut-insert-stitch editing reaction sequence to insert various carbohydrates and activated hydroxyacids into oligosaccharides.