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Heparan sulfate (HS) glycosaminoglycans are widely expressed on the mammalian cell surfaces and extracellular matrices and play important roles in a variety of cell functions. Studies on the structure–activity relationships of HS have long been hampered by the challenges in obtaining chemically defined HS structures with unique sulfation patterns. Here, we report a new approach to HS glycomimetics based on iterative assembly of clickable disaccharide building blocks that mimic the disaccharide repeating units of native HS. Variably sulfated clickable disaccharides were facilely assembled into a library of mass spec-sequenceable HS-mimetic oligomers with defined sulfation patterns by solution-phase iterative syntheses. Microarray and surface plasmon resonance (SPR) binding assays corroborated molecular dynamics (MD) simulations and confirmed that these HS-mimetic oligomers bind protein fibroblast growth factor 2 (FGF2) in a sulfation-dependent manner consistent with that of the native HS. This work established a general approach to HS glycomimetics that can potentially serve as alternatives to native HS in both fundamental research and disease models. 

Abstract The ribosome is a biomolecular machine that undergoes multiple large-scale structural rearrangements during protein elongation. Here, we focus on a conformational rearrangement during translocation, known as P/E hybrid-state formation. Using a model that explicitly represents all non-hydrogen atoms, we simulated more than 120 spontaneous transitions, where the tRNA molecule is displaced between the P and E sites of the large subunit. In addition to predicting a free-energy landscape that is consistent with previous experimental observations, the simulations reveal how a six-residue gate-like region can limit P/E formation, where sub-angstrom structural perturbations lead to an order-of-magnitude change in kinetics. Thus, this precisely defined set of residues represents a novel target that may be used to control functional dynamics in bacterial ribosomes. This theoretical analysis establishes a direct relationship between ribosome structure and large-scale dynamics, and it suggests how next-generation experiments may precisely dissect the energetics of hybrid formation on the ribosome. 

Abstract Rechargeable Mg batteries are a promising energy storage technology to overcome the limitations inherent to Li ion batteries. A critical challenge in advancing Mg batteries is the lack of suitable cathode materials. In this work, we report a cathode design that incorporates S functionality into two‐dimensional metal‐organic‐frameworks (2D‐MOFs). This new cathode material enables good Mg²⁺storage capacity and outstanding cyclability. It was found that upon the initial Mg²⁺insertion and disinsertion, there is an apparent structural transformation that crumbles the layered 2D framework, leading to amorphization. The resulting material serves as the active material to host Mg²⁺through reduction and/or oxidation of S and, to a limited extent, O. The reversible nature of S and O redox chemistry was confirmed by spectroscopic characterizations and validated by density functional calculations. Importantly, during the Mg²⁺insertion and disinsertion process, the 2D nature of the framework was maintained, which plays a key role in enabling the high reversibility of the MOF cathode. 

Abstract Mg‐S batteries hold great promise as a potential alternative to Li‐based technologies. Their further development hinges on solving a few key challenges, including the lower capacity and poorer cycling performance when compared to Li counterparts. At the heart of the issues is the lack of knowledge on polysulfide chemical behaviors in the Mg‐S battery environment. In this Review, a comprehensive overview of the current understanding of polysulfide behaviors in Mg‐S batteries is provided. First, a systematic summary of experimental and computational techniques for polysulfide characterization is provided. Next, conversion pathways for Mg polysulfide species within the battery environment are discussed, highlighting the important role of polysulfide solubility in determining reaction kinetics and overall battery performance. The focus then shifts to the negative effects of polysulfide shuttling on Mg‐S batteries. The authors outline various strategies for achieving an optimal balance between polysulfide solubility and shuttling, including the use of electrolyte additives, polysulfide‐trapping materials, and dual‐functional catalysts. Based on the current understanding, the directions for further advancing knowledge of Mg polysulfide chemistry are identified, emphasizing the integration of experiment with computation as a powerful approach to accelerate the development of Mg‐S battery technology.