TEAD–YAP Interaction Inhibitors and MDM2 Binders from DNA-Encoded Indole-Focused Ugi Peptidomimetics

DNA-encoded combinatorial synthesis provides efficient and dense coverage of chemical space around privileged molecular structures. The indole side chain of tryptophan plays a prominent role in key, or “hot spot”, regions of protein–protein interactions. A DNA-encoded combinatorial peptoid library was designed based on the Ugi four-component reaction by employing tryptophan-mimetic indole side chains to probe the surface of target proteins. Several peptoids were synthesized on a chemically stable hexathymidine adapter oligonucleotide “hexT”, encoded by DNA sequences, and substituted by azide-alkyne cycloaddition to yield a library of 8112 molecules. Selection experiments for the tumor-relevant proteins MDM2 and TEAD4 yielded MDM2 binders and a novel class of TEAD-YAP interaction inhibitors that perturbed the expression of a gene under the control of these Hippo pathway effectors.     

Atomic-Scale Insight into Exsolution of CoFe Alloy Nanoparticles in La0.4Sr0.6Co0.2Fe0.7Mo0.1O3−δ with Efficient CO2 Electrolysis

In situ exsolution of metal nanoparticles in perovskite under reducing atmosphere is employed to generate a highly active metal–oxide interface for CO₂ electrolysis in a solid oxide electrolysis cell. Atomic-scale insight is provided into the exsolution of CoFe alloy nanoparticles in La_0.4Sr_0.6Co_0.2Fe_0.7Mo_0.1O_3−δ (LSCFM) by in situ scanning transmission electron microscopy (STEM) with energy-dispersive X-ray spectroscopy and DFT calculations. The doped Mo atoms occupy B sites of LSCFM, which increases the segregation energy of Co and Fe ions at B sites and improves the structural stability of LSCFM under a reducing atmosphere. In situ STEM measurements visualized sequential exsolution of Co and Fe ions, formation of CoFe alloy nanoparticles, and reversible exsolution and dissolution of CoFe alloy nanoparticles in LSCFM. The metal–oxide interface improves CO₂ adsorption and activation, showing a higher CO₂ electrolysis performance than the LSCFM counterparts.     

Rational Design of the Metal-Free KBe2BO3F2⋅(KBBF) Family Member C(NH2)3SO3F with Ultraviolet Optical Nonlinearity

The first fluorosulfonic ultraviolet (UV) nonlinear optical (NLO) material, C(NH₂)₃SO₃F, is rationally designed by taking KBe₂BO₃F₂ (KBBF) as the parent compound. C(NH₂)₃SO₃F features similar topological layers as KBBF by replacing inorganic (BO₃)³⁻ with organic C(NH₂)₃⁺ trigonal units and BeO₃F with SO₃F⁻ tetrahedra. Therefore, C(NH₂)₃SO₃F is a metal-free UV NLO crystal. Benefiting from the coplanar configuration of the C(NH₂)₃⁺ cationic groups, it possesses a large SHG response of 5×KDP and moderate birefringence of 0.133@1064 nm. Besides, it has a short UV cutoff edge of 200 nm. The calculated results reveal the shortest SHG phase-matching wavelengths can reach 200 nm. These findings highlight the exploration of metal-free compounds as nontoxic and low-cost UV NLO materials as a new research area.