Wubailey0173

Clickmers are chemically modified aptamers representing an innovative reagent class for developing binders for biomolecules with great impact on therapeutic and diagnostic applications. To establish a novel layer for screening various chemical entities, we developed a split-combine selection strategy simultaneously enriching for clickmers having different modifications. Due to the inherent design of this strategy, dynamic changes of DNA populations are traceable at an individual sequence level. Besides off-rate guided enrichment, the process makes the survival of the sequences most adapted to the applied selection condition observable. The underlying strategy provides unprecedented molecular insight into the selection process, based on which more sophisticated procedures will become pliable in the future.The reversible reaction of H2 with a bis-phosphenium complex of chromium provides a rare example of 3d transition metal/phosphenium cooperativity. Photolysis induces the activation of H2 and yields a spectroscopically detectable phosphenium-stabilized (σ-H2)-complex, readily showing exchange with gaseous H2 and D2. Further reaction of this complex affords a phosphine-functionalized metal hydride, representing a unique example of reversible H2 cleavage across a 3d M[double bond, length as m-dash]P bond. The same species is also accessible via stepwise H+/H- transfer to the bis-phosphenium complex, and releases H2 upon heating or irradiation. Dihydrogen transfer from the H2-complex to styrene is exploited to demonstrate the first example of promoting hydrogenation with a phosphenium complex.We propose a nanoplasmonic platform that can be used for sensing trace levels of heavy metals in solutions via simple optical reflectivity measurements. The considered example is a lead sensor, which relies on the lead-mediated assembly of glutathione-functionalized gold nanoparticles (NPs) at a self-healing water/DCE liquid | liquid interface (LLI). Capillary forces tend to trap each NP at the LLI while the negatively charged ligands prevent the NPs settling too close to each other. In the presence of lead, due to chelation between the lead ion and glutathione ligand, the NPs assemble into a dense quasi-2D interfacial array. Such a dense assembly of plasmonic NPs can generate a remarkable broad-band reflectance signal, which is absent when NPs are adsorbed at the interface far apart from each other. The condensing effect of the LLI and the plasmonic coupling effect among the NP array gives rise to a dramatic enhancement of the reflectivity signals. Importantly, we show that our theory of the optical reflectivity from such an array of NPs works in perfect harmony with the physics and chemistry of the system with the key parameter being the interparticle distance at the interface. As a lead sensor, the system is fast, stable, and can achieve detection limits down to 14 ppb. Future alternative recognizing ligands can be used to build sister platforms for detecting other heavy metals.Overcoming resistance to bioactive small molecules is a significant challenge for health care and agriculture. As a result, efforts to uncover the mechanisms of resistance are essential to the development of new antibiotics, anticancer drugs and pesticides. To study how nature evolves resistance to highly potent natural products, we examined the biosynthesis and mechanism of self-resistance of the fungal glyceraldehyde-3-phosphate dehydrogenase (GAPDH) inhibitor heptelidic acid (HA). HA is a nanomolar inhibitor of GADPH through the covalent modification of the active site cysteine thiol. The biosynthetic pathway of HA was elucidated, which uncovered the enzymatic basis of formation of the epoxide warhead. Structure-activity relationship study using biosynthetic intermediates established the importance of the fused lactone ring system in HA. The molecular basis of HA inhibiting human GAPDH was illustrated through the crystal structure of Hs-GAPDH covalently bound with HA. A GAPDH isozyme HepG encoded in the HA cluster was characterized to be less sensitive to HA, and therefore contribute to self-resistance for the producing host. Comparison of the crystal structures of human GAPDH and HepG showed mutations both within and remote to the active site can contribute to resistance of inactivation, which was confirmed through mutagenesis. Due to the critical role GAPDH plays in aerobic glycolysis and other cellular functions, knowledge of HA mode of action and self-resistance mechanism could accelerate the development of improved inhibitors.The electrochemical CO2 reduction reaction (CO2RR) on RuO2 and RuO2-based electrodes has been shown experimentally to produce high yields of methanol, formic acid and/or hydrogen while methane formation is not detected. This CO2RR selectivity on RuO2 is in stark contrast to copper metal electrodes that produce methane and hydrogen in the highest yields whereas methanol is only formed in trace amounts. learn more Density functional theory calculations on RuO2(110) where only adsorption free energies of intermediate species are considered, i.e. solvent effects and energy barriers are not included, predict however, that the overpotential and the potential limiting step for both methanol and methane are the same. In this work, we use both ab initio molecular dynamics simulations at room temperature and total energy calculations to improve the model system and methodology by including both explicit solvation effects and calculations of proton-electron transfer energy barriers to elucidate the reaction mechanism towards several CO2RR products methanol, methane, formic acid, CO and methanediol, as well as for the competing H2 evolution. We observe a significant difference in energy barriers towards methane and methanol, where a substantially larger energy barrier is calculated towards methane formation than towards methanol formation, explaining why methanol has been detected experimentally but not methane. Furthermore, the calculations show why RuO2 also catalyzes the CO2RR towards formic acid and not CO(g) and methanediol, in agreement with experimental results. However, our calculations predict RuO2 to be much more selective towards H2 formation than for the CO2RR at any applied potential. Only when a large overpotential of around -1 V is applied, can both formic acid and methanol be evolved, but low faradaic efficiency is predicted because of the more facile H2 formation.