FIP200 Methylation by SETD2 Prevents Trim21-Induced Degradation and Preserves Autophagy Initiation

FIP200, also known as RB1CC1, is a protein that assembles the autophagy initiation complex. Its post-translational modifications and degradation mechanisms are unclear. Upon autophagy activation, we find that FIP200 is methylated at lysine1133 (K1133) by methyltransferase SETD2. We identify the E3 ligase Trim21 to be responsible for FIP200 ubiquitination by targeting K1133, resulting in FIP200 degradation through the ubiquitin–proteasome system. SETD2-induced methylation blocks Trim21-mediated ubiquitination and degradation, preserving autophagy activity. SETD2 and Trim21 orchestrate FIP200 protein stability to achieve dynamic and precise control of autophagy flux

Catalytic Cyclopropanol Ring Opening for Divergent Syntheses of γ‑Butyrolactones and δ‑Ketoesters Containing All-Carbon Quaternary Centers

Catalytic ring opening cross coupling reactions of strained cyclopropanols have been useful for the syntheses of various β-substituted carbonyl products. Among these ring opening cross coupling reactions, the formation of α,β-unsaturated enone byproducts often competes with the desired cross coupling processes and has been a challenging synthetic problem to be addressed. Herein, we describe our efforts in developing divergent syntheses of a wide range of γ-butyrolactones and δ-ketoesters containing all-carbon quaternary centers via copper-catalyzed cyclopropanol ring opening cross couplings with 2-bromo-2,2-dialkyl esters. Our mechanistic studies reveal that unlike the previously reported cases, the formation of α,β-unsaturated enone intermediates is actually essential for the γ-butyrolactone synthesis and also contributes to the formation of the δ-ketoester product. The γ-butyrolactone synthesis is proposed to go through an intermolecular radical conjugate addition to the in situ generated α,β-unsaturated enone followed by an intramolecular radical cyclization to the ester carbonyl double bond. The reactions are effective to build all-carbon quaternary centers and have broad substrate scope

Efficient Synthesis of β‑CF₃/SCF₃‑Substituted Carbonyls via Copper-Catalyzed Electrophilic Ring-Opening Cross-Coupling of Cyclopropanols

The first copper-catalyzed ring-opening electrophilic trifluoromethylation and trifluoromethylthiolation of cyclopropanols to form C_sp3–CF₃ and C_sp3–SCF₃ bonds have been realized. These transformations are efficient for the synthesis of β-CF₃- and β-SCF₃-substituted carbonyl compounds that are otherwise challenging to access. The reaction conditions are mild and tolerate a wide range of functional groups. Application to a concise synthesis of LY2409021, a glucagon receptor antagonist that is used in clinical trials for type 2 diabetes mellitus, is reported as well

Surface-Enhanced Raman Scattering from Synergistic Contribution of Metal and Semiconductor in TiO₂/MBA/Ag(Au) and Ag(Au)/MBA/TiO₂ Assemblies

Traditional metal SERS-active substrate (Ag or Au) and novel semiconductor SERS-active substrate (TiO₂) are combined into the composite system for their synergetic contribution to SERS. A series of assemblies with 4-mercaptobenzoic acid (4-MBA) molecule, TiO₂, and/or Ag (Au) nanoparticles (NPs) have been fabricated by a self-assembly method. In the sandwich-structure assemblies (TiO₂/MBA/Ag­(Au) and Ag­(Au)/MBA/TiO₂), the SERS signals of 4-MBA molecule exhibit obvious difference in not only the intensity but also Raman frequency as compared with that SERS enhancement in the TiO₂/MBA, which is attributed to the introduce of metals and its interaction/synergistic action with TiO₂ NPs. SERS enhancement behaviors of 4-MBA in the sandwich-structure assemblies strongly depend on the natures of metals and 4-MBA molecule, which can result in a influence on the TiO₂-to-molecule charge transfer and consequent additional EM field effect. This work would like to be interesting and of considerable value for both theory development and practice application of SERS technology

Interfacial Charge-Transfer Effects in Semiconductor–Molecule–Metal Structures: Influence of Contact Variation

The charge-transfer resonance of Raman measurements in nanosized semiconductor–molecule–metal interfaces as a function of the excitation energy with four models (Cu–ZnO–PATP–Ag, Cu–Ag–PATP–ZnO, Cu–ZnO–Ag–PATP, and Cu–Ag–ZnO–PATP assemblies) to describe this dependence provides a powerful tool to study the chemical mechanism of surface enhanced Raman scattering (SERS). We measured the SERS spectra of self-assembled p-aminothiophenol (PATP) molecule junctions at 488, 514, 633, and 785 nm excitation wavelengths. We followed changes at the molecule junctions during the conditioning and eventually effect of charge-transfer (CT) through molecule–ZnO interfaces. Our results demonstrate that the interaction between the semiconductor bands and molecular energy levels can lead to novel charge behavior. The typical ZnO-PATP interfacial electron–hole recombination causes an increase in the CT resonance enhancement of Raman scattering, which is mainly responsible for the drastic change in molecular polarizability. We also proposed a complementary interpretation of the mechanism responsible for the highly variable enhancement observed in SERS