A New Strategy for Efficient Synthesis of Medium and Large Ring Lactones without High Dilution or Slow Addition

We have developed an efficient method for medium and large ring lactone synthesis by a conceptually different ring-expansion strategy. The design of an unprecedented ring conjunction mode of oxetene, combined with the appropriate choice of a Lewis acid promoter and an additive, constitutes the key components of the new process. Enabled by this new approach, the reaction does not require high dilution or slow addition

A New Strategy for Efficient Synthesis of Medium and Large Ring Lactones without High Dilution or Slow Addition

We have developed an efficient method for medium and large ring lactone synthesis by a conceptually different ring-expansion strategy. The design of an unprecedented ring conjunction mode of oxetene, combined with the appropriate choice of a Lewis acid promoter and an additive, constitutes the key components of the new process. Enabled by this new approach, the reaction does not require high dilution or slow addition

Presentation_1_Autophosphorylation Mechanism of the Ser/Thr Kinase Stk1 From Staphylococcus aureus.pdf

<p>The eukaryotic-like Ser/Thr kinase Stk1 is crucial for virulence, cell wall biosynthesis, and drug susceptibility in methicillin-resistant Staphylococcus aureus (S. aureus) (MRSA). Importantly, MRSA lacking Stk1 become sensitive to β-lactam antibiotics, implying that Stk1 could be an alternative target for combination therapy. However, the autophosphorylation mechanism of Stk1 remains elusive. Using a phosphoproteomic study, we identified six in vivo phosphorylated activation loop residues (Ser159, Thr161, Ser162, Thr164, Thr166, and Thr172) of Stk1, which are also phosphorylated in vitro. We further showed that cis autophosphorylation of Thr172 in the GT/S motif is essential for self-activation and kinase activity of Stk1 kinase domain (Stk1-KD), whereas the trans autophosphorylation of other activation loop serines/threonines are required for the optimal kinase activity of Stk1-KD. Moreover, substitution of the activation loop serines/threonines impaired in vivo autophosphorylation activity of kinase variants, while T172A and T172D variants were unable to autophosphorylate in the cellular content, underlining the essential role of Thr172 for Stk1 activity in vivo. This study provides insights into molecular basis for regulation of Stk1 activity from S. aureus.</p

Investigation of Cellular Uptakes of the In-Tether Chiral-Center-Induced Helical Pentapeptides

We recently reported that a precisely positioned in-tether chiral center can modulate backbone peptides’ secondary structures, which provides an unbiased platform to evaluate peptides’ biophysical properties solely imposed by secondary structure differences. In this work, we studied the cellular uptake efficiency and mechanism of epimer pairs of a panel of chirality-induced helical peptides (CIH peptides). Although the peptides’ cellular uptake is a synergetic result of various factors, our results unambiguously indicate that helical content is an important factor for the cellular uptake of CIH peptides

<i>N</i>-Heterocyclic Carbene-Catalyzed Internal Redox Reaction of Alkynals: An Efficient Synthesis of Allenoates

An efficient <i>N</i>-heterocyclic carbene (NHC)-catalyzed internal redox reaction of alkynals that bear a γ leaving group has been developed. This process provides a new access to a range of allenoates in good yields. Preliminary results demonstrate that the enantioselective variant can also be achieved

4‑Iodine <i>N</i>‑Methylpyridinium-Mediated Peptide Synthesis

Through systematic optimization of halopyridinium compounds, we established a peptide coupling protocol utilizing 4-iodine N-methylpyridinium (4IMP) for solid-phase peptide synthesis (SPPS). The 4IMP coupling reagent is easily prepared, bench stable, and cost-effective. Employing 4IMP in the SPPS process has showcased remarkable chemoselectivity and efficiency, effectively eliminating racemization and epimerization. This achievement has been substantiated through the successful synthesis of a range of peptides via the direct utilization of commercially available amino acid substrates for SPPS

Dual In-Tether Chiral Centers Modulate Peptide Helicity

The facile chemical modification on the peptide cross-linking moiety is an important strategy for improving the physicochemical properties of a peptide. Herein, peptides were constrained into helical conformations via the synergistic effects of dual in-tether chiral centers. A pentapeptide minimalistic model was used to determine the correlation between the absolute configurations of the dual in-tether chiral centers and the secondary structures of the peptides. This strategy provides an on-tether modification site that does not interrupt the secondary structure of the peptide

Knockdown of BCRP/ABCG2 expression by V-BCRPi in JAR cells using immunofluorescence analysis (×100).

<p>The results for experimental groups 1 to 8 are shown: 1: mock cells with MoAb or 2: PBS or cells infected with 3: V-BCRP1i, 4: V-BCRP1i-c, 5: V-BCRP2i, 6: V-BCRP2i-c, 7: V-BCRP3i, or 8: V-BCRP3i-c. The fluorescence intensity of cells subjected to V-BCRP3i treatment was the lowest.</p

Additional file 1 of Single-domain antibodies against SARS-CoV-2 RBD from a two-stage phage screening of universal and focused synthetic libraries

Supplementary Material

Changes in tumor weight and volume and the anti-tumor rate in transplantation tumors in nude mice after virus infection and drug treatment (x±s, n = 15).

<p>*: PBS+5-FU vs. V-BCRPi+5-FU, p<0.01.</p