Many antimicrobial peptides (AMPs) exert their activity by disrupting the integrity of the bacterial plasma membrane. One of the membrane-disrupting mechanisms of AMPs involves the formation of toroidal pores, composed of α-helices and lipid headgroups. These pores enable the diffusion of lipid molecules to the opposite leaflet without exposing their headgroups to the hydrocarbon core. Consequently, an increase in lipid transbilayer diffusion (flip-flop) in the presence of AMPs is an important characteristic for AMP structure and function. However, real-time monitoring of the rapid flip-flop in the presence of transmembrane pores has not been achieved because of the permeation of membrane-impermeable reagents and/or the low time resolution of the conventional assays. Herein, we have developed a fluorescence quenching-based flip-flop assay. The flip-flop rates obtained by our method were consistent with those measured by the conventional dithionite reduction assay, confirming the reliability of our approach. The real-time monitoring of the flip-flop process in the presence of the AMP, magainin 2, using the self-quenching assay suggested that the disordered toroidal pores composed of 2 magainin molecules facilitate flip-flop. The newly developed assay will provide a better understanding of the interactions between AMPs and lipid bilayers.

For the production of active pharmaceutical ingredients through sustainable organic synthesis, the use of inexpensive and non-toxic catalysts is desirable. Recently, homogeneous chiral Fe catalysts have received considerable attention as tools for achieving this goal. However, chiral Fe catalysts often perform poorly when used to synthesize complex molecules, limiting their application to large-scale syntheses. In this study, we developed an asymmetric sulfoxidation reaction for the production of esomeprazole at a pilot-plant scale. The reaction uses a catalytic system generated in situ from an Fe salt, which is abundant, inexpensive, and environmentally friendly, combined with a chiral Schiff ligand and a carboxylate salt, and hydrogen peroxide as the oxidant. Subsequently, the obtained esomeprazole is converted from its K-salt form to an Mg-salt, thereby establishing a manufacturing process that yields high-purity active pharmaceutical ingredients with impurities controlled to less than 0.05%. The enantioselectivity and kinetic resolution of the asymmetric sulfoxidation reaction are dependent on the spatial relationship between the sp³-hybridization center and the sp² carbon adjacent to the substituent attached to the S atom of the substrate. We also speculate that the carboxylic acid additive plays a critical role in activating hydrogen peroxide through heterolytic cleavage and enabling the formation of both mono- and dinuclear iron oxidants. Furthermore, we propose a catalytic mechanism for this enantioselective oxidation reaction.

Three new acylated glycosidic acid methyl esters and one known compound were isolated by treating the crude resin glycoside fraction derived from the seeds of Ipomoea lacunosa with indium(III) chloride in methanol, and their structures were elucidated using spectroscopic methods. The new compounds contained methyl 3S,11S-dihydroxytetradecanoate as the aglycone. Two were hexaglycosides and one was a nonaglycoside, with saccharide cores partially acylated by a glycosidic acid, 7S-hydroxydecanoic acid 7-O-β-d-quinovopyranoside (quamoclinic acid B), and/or organic acids, including isobutyric and 2S-methylbutyric acids. Furthermore, the cytotoxic activities of the isolated compounds against HL-60 human promyelocytic leukemia cells were evaluated, and they exhibited moderate activities.

Lysosome-targeting chimera (LYTAC) efficiently degrades specific membrane proteins. In a previous study, we synthesized and reported human epidermal growth factor receptor 2 (HER2)-LYTAC (that induces the degradation of HER2 protein using DNA aptamers that binds to insulin-like growth factor receptor 2 and HER2). In this study, we designed and synthesized linker-length-modified HER2-LYTAC derivatives with varying distances between the DNA aptamers and assessed their protein degradation-inducing activity. The results revealed that HER2 degradation varied significantly with the linker length. Notably, HL5L—HER2-LYTAC with a 5-bp longer linker than that of the original HER2-LYTAC—exhibited equivalent or enhanced activity and significantly inhibited the proliferation of HER2-positive cancer cells. This is the first study to assess the effect of linker length in designing LYTAC molecules using bispecific DNA aptamers and offers valuable insights into the molecular design of nucleic acid-based LYTACs.