Research articles

Gangliosides are composed of oligosaccharide chains attached to ceramides and are employed as targeted drugs and diagnostic biomarkers, however, their industrially-relevant synthesis remains challenging. Here, the authors develop a modular chemoenzymatic cascade assembly strategy for the customized and large-scale synthesis of ganglioside analogues with various glycan and ceramide epitopes.

Protein binding plays an important role in the function and design of protein complexes, however, the relationships among protein sequences, structures, and interactions shaped by evolution remain underexplored. Here, the authors use computational simulations to study the binding specificity of a two-component system under protein sequence evolution and reveal that the binding specificity is modulated by both direct intermolecular interactions and long-range epistasis across the binding complex.

Capsid proteins (CPs) of various icosahedral and rod-shaped viruses exhibit structural diversity and tunability as well as application in smart hybrid nanoparticles, however, the potential of CPs of filamentous plant viruses remains underexplored. Here, the authors exploit the structure-based design of CP from potato virus Y to tune the shape, size, RNA encapsidation ability, symmetry, stability, and surface functionalization of nanoparticles.

Descriptor design in catalyst informatics necessitates adequate prior knowledge for delving into unknown territories, particularly when confronted with limited data, thus presenting a logical contradiction. Here, the authors report a technique for automatic feature engineering that works on small catalyst datasets without reliance on pre-existing knowledge about the target catalysis.

High resolution force measurements of molecules on surfaces using non-contact atomic force microscopy are typically performed at cryogenic temperatures. Here, the authors outline a reliable protocol for acquiring three-dimensional force map data at room temperature, demonstrating such capabilities on isolated cobalt phthalocyanine molecules and islands of C60 molecules.

Inositol requiring enzyme 1 (IRE1) is a conserved protein kinase involved in the endoplasmic reticulum secretory pathway, however, IRE1 from S. cerevisiae and human show opposite responses to flavonoid quercetins. Here, the authors apply in silico and in vitro approaches to reveal the different binding modes of quercetins on IRE1, providing molecular insight into their opposite effects on S. cerevisiae and humans.

Pyrroles are an important scaffold in medicinal chemistry with various bioactivities; however, the selective chemical halogenation of pyrroles remains challenging. Here, the authors develop an enzymatic site-selective chlorination of pyrrolic heterocycles by a flavin-dependent halogenase PrnC and apply it to the chemoenzymatic synthesis of a chlorinated analogue of the fungicide Fludioxonil.

Peptide-based coacervates display interesting properties for biomedical applications, however, the link between peptide structure and coacervate material properties remains unclear. Here, the authors report a direct correlation between the primary and secondary structures of the peptides and the viscoelastic properties of the coacervates.

Sulfatinib is a multi-target angio-immuno kinase inhibitor for treating neuroendocrine tumors, selectively targeting FGFR1 and CSF-1R. Here, the authors elucidate the molecular mechanisms behind its binding and kinase selectivity, highlighting interactions with a hydrophobic pocket for FGFR selectivity, and rotatory flexibility to potentially overcome CSF-1R^T663I gatekeeper mutation.

Colloidal nanocrystals find applications from electronics to catalysis and biological sensors, but their complex surface structures are challenging to explore. Here, the authors use graphene liquid cell transmission electron microscopy to show that solubilized platinum crystals of less than 3 nm in size have individual, ordered cores surrounded by mobile surface atoms.

Dual asymmetric catalysis is powerful for the synthesis of multi-stereocenter molecules, however, the integration of dual catalysts remains challenging due to the intrinsic deactivation of dual-species and extrinsic conflict of reaction conditions. Here, the authors develop a compartmental and thermoresponsive poly(N-isopropylacrylamide)-hydrogel-supported bifunctional catalyst to overcome these challenges.

Natural products are a rich source of lead compounds in drug discovery. Here, the authors report the discovery and synthesis of five nitrogenous polycyclic polyprenylated acylphloroglucinols named hyperelanitriles A–D and hyperelamine A from the plant Hypericum elatoides with anti-inflammatory activity against lipopolysaccharides-activated nitric oxide production.