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Oligomers of benzoylalanine-based amidothioureas containing four β-turn structures spaced by meta-substituted benzenes were shown to undergo assembly in dilute CH3CN solution into supramolecular helices of enhanced supramolecular helicity, whereas those spaced by para-substituted benzene spacer(s) or those spaced by meta-substituted benzenes but with one or two β-turns exhibit a substantially decreased tendency of assembling. [ABSTRACT FROM AUTHOR]

The development of stimuli‐responsive artificial H+/Cl− ion channels, capable of specifically disturbing the intracellular ion homeostasis of cancer cells, presents an intriguing opportunity for achieving high selectivity in cancer therapy. Herein, we describe a novel family of non‐covalently stapled self‐assembled artificial channels activatable by biocompatible visible light at 442 nm, which enables the co‐transport of H+/Cl− across the membrane with H+/Cl− transport selectivity of 6.0. Upon photoirradiation of the caged C4F‐L for 10 min, 90 % of ion transport efficiency can be restored, giving rise to a 10.5‐fold enhancement in cytotoxicity against human colorectal cancer cells (IC50=8.5 μM). The mechanism underlying cancer cell death mediated by the H+/Cl− channels involves the activation of the caspase 9 apoptosis pathway as well as the scarcely reported disruption of the autophagic processes. In the absence of photoirradiation, C4F‐L exhibits minimal toxicity towards normal intestine cells, even at a concentration of 200 μM. [ABSTRACT FROM AUTHOR]

We report the first example of C-I···π halogen bonding driven supramolecular helix in highly dilute solution of micromolar concentration, using alanine based bilateral I-substituted N-amidothioureas that contain helical fragments, the β-turn structures. The halogen bonding interactions afford head-to-tail linkages that help to propagate the helicity of the helical fragments. In support of this action of the halogen bonding, chiral amplification was observed in the supramolecular helix formed in acetonitrile solution. The present finding provides alternative tools in the design of self-assembling macromolecules. [ABSTRACT FROM AUTHOR]

Developing chiral assemblies that mimic biological secondary structures, e.g., protein β-sheet, α-helix, and DNA double helix, is a captivating goal in supramolecular chemistry. Here, we create a family of biomimetic chiral assemblies from alanine-based peptidomimetics, wherein the incorporation of N -terminal 2,1,3-benzoselenadiazole groups enables the rarely utilized chalcogen bonding as the adhesive interaction. While the alanine-based acylhydrazine molecule 1L was designed as a building unit with an extended conformation, simple derivatization of 1L affords folded unilateral N -amidothiourea 2L with one β-turn and bilateral N -amidothiourea 3L with two β-turns. This derivatization leads to the evolution of molecular assemblies from β-sheet organization ( 1L ) to single helix (α-helix mimic, 2L ) and ultimately to double helix ( 3L ), illustrating an evolutionary route relating the structures and superstructures. In the case of the double helix formed by 3L , an unexpected cis -form that brings the two β-turns into one side was observed, stabilized via the π···π interaction between two N -terminal 2,1,3-benzoselenadiazole groups. This conformation allows double-crossed N-Se···S═C chalcogen bonds to support a DNA-like P -double helix featuring intrastrand noncovalent interactions and interstrand covalent linkages, surviving in both the solid state and in dilute acetonitrile solution phase.

The development of stimuli-responsive artificial H + /Cl - ion channels, capable of specifically disturbing the intracellular ion homeostasis of cancer cells, presents an intriguing opportunity for achieving high selectivity in cancer therapy. Herein, we describe a novel family of non-covalently stapled self-assembled artificial channels activatable by biocompatible visible light at 442 nm, which enables the co-transport of H + /Cl - across the membrane with H + /Cl - transport selectivity of 6.0. Upon photoirradiation of the caged C4F-L for 10 min, 90 % of ion transport efficiency can be restored, giving rise to a 10.5-fold enhancement in cytotoxicity against human colorectal cancer cells (IC 50 =8.5 μM). The mechanism underlying cancer cell death mediated by the H + /Cl - channels involves the activation of the caspase 9 apoptosis pathway as well as the scarcely reported disruption of the autophagic processes. In the absence of photoirradiation, C4F-L exhibits minimal toxicity towards normal intestine cells, even at a concentration of 200 μM., (© 2023 Wiley-VCH GmbH.)

Spontaneous resolution leading to conglomerate crystals remains a significant challenge. Here we propose the formation of orthogonal homochiral supramolecular helices in at least two dimensions to allow spontaneous resolution. We suggest the design rationale that the chiral species is made into helical building blocks to allow the helix formation. As a proof-of-concept, acetylalanine was made into a helical short azapeptide, its N-amidothiourea derivative containing a β-turn structure, to which a halogen atom was further introduced at the phenylthiourea aromatic ring. The resultant folded species undergoes both intermolecular hydrogen and halogen bonding across the turn structure to form orthogonal intermolecular hydrogen-bonded and halogen-bonded supramolecular helices in two dimensions, and undergoes chiral resolution upon crystallization. Meanwhile, counterparts containing either an F-substituent with weak halogen bonding or no halogen atom crystallize as racemic compounds., (© 2022 Wiley-VCH GmbH.)

Gastric cancer (GC) is a malignant tumor with an adverse health effect worldwide, whereas the underlying mechanism of GC development remains controversial. Identification of biomarkers is critical for the treatment of GC. Increasing evidence demonstrates that protein modification plays a pivotal role in carcinogenesis. USP38 is a member of the ubiquitin-specific protease (USP) family, which promotes protein stability by deubiquitinating the target proteins. In this study, we focused on the effect of USP38 on the GC and explored its underlying mechanism. The Cancer Genome Atlas (TCGA) database was used to evaluate the expression of USP38. AGS and HGC27 cells were treated with siRNA targeting USP38 or plasmids overexpressing USP38 to disturb levels of USP38. Immumohistochemical staining was performed to detect the level of USP38 and FASN. RT-qPCR and Western blotting (WB) were used to analyze the expression of mRNA and protein respectively. CCK8 assay, colony formation, cell migration assay, and cell apoptosis and cell cycle were performed to assess cell proliferation and migration ability. A subcutaneous tumor mice model was carried to verify the effect of USP38 on the GC in vivo. In this research, we found that USP38 was overexpressed in GC tissues, and USP38 contributed to GC cell proliferation, migration and tumorigenesis. Cell cycle and apoptosis were also regulated by USP38. Mechanistically, USP38 interacted with FASN, which resulted in enhanced protein stability of FASN and increased triglyceride production. Furthermore, FASN was critical for GC cell growth, migration and tumor development triggered by USP38 overexpression because its inhibitor orilistat reversed phenotypes in USP38 overexpressed GC cells. Collectively, USP38 overexpression is critical for GC cell growth, migration and tumorigenesis. Targeting FASN with inhibitors could be used as a potential treatment for GC patients with highly expressed USP38., Competing Interests: None., (AJCR Copyright © 2022.)