Ethoxyfagaronine, a synthetic analogue of fagaronine that inhibits vascular endothelial growth factor-1, as a new anti-angiogeneic agent

Angiogenesis plays a pivotal role in tumorigenesis and also contributes to the pathogenesis of hematologic malignancies. A number of plant compounds have shown efficacy in preclinical and clinical studies and some of them possess an anti-angiogenic activity. Our present findings report anti-angiogenic activities of ethoxyfagaronine (etxfag), a synthetic derivative of fagaronine. Once determined the non-cytotoxic concentration of etxfag, we showed that the drug inhibits VEGF-induced angiogenesis in a Matrigel™ plug assay and suppresses ex vivo sprouting from VEGF-treated aortic rings. Each feature leading to neovascularization was then investigated and results demonstrate that etxfag prevents VEGF-induced migration and tube formation in human umbilical vein endothelial cells (HUVEC). Moreover, etxfag also suppresses VEGF-induced VEGFR-2 phosphorylation and inhibits FAK phosphorylation at Y-861 as well as focal adhesion complex turnover. Beside these effects, etxfag modifies MT1-MMP localization at the endothelial cell membrane. Finally, immunoprecipitation assay revealed that etxfag decreases VEGF binding to VEGFR-2. As we previously reported that etxfag is able to prevent leukemic cell invasiveness and adhesion to fibronectin, all together our data collectively support the anti-angiogenic activities of etxfag which could represent an additional approach to current anti-cancer therapies

Harnessing a Biocatalyst to Bioremediate the Purification of Alkylglycosides

Wahart et al. demonstrate the use of an immobilised oxidase enzyme coupled to an extractive amino resin for the bioremediation of a common industrial surfactant. This allows the facile purification of alkyl monoglucosides without the need for high energy distillations. More information can be found in the Research Article by G. J. Miller, S. C. Cosgrove et al

Harnessing a Biocatalyst to Bioremediate the Purification of Alkylglycosides.

As the world moves towards net-zero carbon emissions, the development of sustainable chemical manufacturing processes is essential. Within manufacturing, purification by distillation is often used, however this process is energy intensive and methods that could obviate or reduce its use are desirable. Developed herein is an alternative, oxidative biocatalytic approach that enables purification of alkyl monoglucosides (essential bio-based surfactant components). Implementing an immobilised engineered alcohol oxidase, a long-chain alcohol by-product derived from alkyl monoglucoside synthesis (normally removed by distillation) is selectively oxidised to an aldehyde, conjugated to an amine resin and then removed by simple filtration. This affords recovery of the purified alkyl monoglucoside. The approach lays a blueprint for further development of sustainable alkylglycoside purification using biocatalysis and, importantly, for refining other important chemical feedstocks that currently rely on distillation. [Abstract copyright: © 2023 The Authors. ChemBioChem published by Wiley-VCH GmbH.

Reverse thiophosphorylase activity of a glycoside phosphorylase in the synthesis of an unnatural Manβ1,4GlcNAc library

β-Mannosides are ubiquitous in nature, with diverse roles in many biological processes. Notably, Manβ1,4GlcNAc a constituent of the core N-glycan in eukaryotes was recently identified as an immune activator, highlighting its potential for use in immunotherapy. Despite their biological significance, the synthesis of β-mannosidic linkages remains one of the major challenges in glycoscience. Here we present a chemoenzymatic strategy that affords a series of novel unnatural Manβ1,4GlcNAc analogues using the β-1,4-D-mannosyl-N-acetyl-D-glucosamine phosphorylase, BT1033. We show that the presence of fluorine in the GlcNAc acceptor facilitates the formation of longer β-mannan-like glycans. We also pioneer a “reverse thiophosphorylase” enzymatic activity, favouring the synthesis of longer glycans by catalysing the formation of a phosphorolysis-stable thioglycoside linkage, an approach that may be generally applicable to other phosphorylases

Reverse thiophosphorylase activity of a glycoside phosphorylase in the synthesis of an unnatural Manβ1,4GlcNAc library

β-Mannosides are ubiquitous in nature, with diverse roles in many biological processes. Notably, Manβ1,4GlcNAc a constituent of the core N-glycan in eukaryotes was recently identified as an immune activator, highlighting its potential for use in immunotherapy. Despite their biological significance, the synthesis of β-mannosidic linkages remains one of the major challenges in glycoscience. Here we present a chemoenzymatic strategy that affords a series of novel unnatural Manβ1,4GlcNAc analogues using the β-1,4-D-mannosyl-N-acetyl-D-glucosamine phosphorylase, BT1033. We show that the presence of fluorine in the GlcNAc acceptor facilitates the formation of longer β-mannan-like glycans. We also pioneer a “reverse thiophosphorylase” enzymatic activity, favouring the synthesis of longer glycans by catalysing the formation of a phosphorolysis-stable thioglycoside linkage, an approach that may be generally applicable to other phosphorylases

Reverse thiophosphorylase activity of a glycoside phosphorylase in the synthesis of an unnatural Manβ1,4GlcNAc library †

β-Mannosides are ubiquitous in nature, with diverse roles in many biological processes. Notably, Manβ1,4GlcNAc a constituent of the core N-glycan in eukaryotes was recently identified as an immune activator, highlighting its potential for use in immunotherapy. Despite their biological significance, the synthesis of β-mannosidic linkages remains one of the major challenges in glycoscience. Here we present a chemoenzymatic strategy that affords a series of novel unnatural Manβ1,4GlcNAc analogues using the β-1,4-d-mannosyl-N-acetyl-d-glucosamine phosphorylase, BT1033. We show that the presence of fluorine in the GlcNAc acceptor facilitates the formation of longer β-mannan-like glycans. We also pioneer a “reverse thiophosphorylase” enzymatic activity, favouring the synthesis of longer glycans by catalysing the formation of a phosphorolysis-stable thioglycoside linkage, an approach that may be generally applicable to other phosphorylases

Identification of CD36 as a new interaction partner of membrane NEU1: potential implication in the pro-atherogenic effects of the elastin receptor complex

In addition to its critical role in lysosomes for catabolism of sialoglycoconjugates, NEU1 is expressed at the plasma membrane and regulates a myriad of receptors by desialylation, playing a key role in many pathophysiological processes. Here, we developed a proteomic approach dedicated to the purification and identification by LC–MS/MS of plasma membrane NEU1 interaction partners in human macrophages. Already known interaction partners were identified as well as several new candidates such as the class B scavenger receptor CD36. Interaction between NEU1 and CD36 was confirmed by complementary approaches. We showed that elastin-derived peptides (EDP) desialylate CD36 and that this effect was blocked by the V14 peptide, which blocks the interaction between bioactive EDP and the elastin receptor complex (ERC). Importantly, EDP also increased the uptake of oxidized LDL by macrophages that is blocked by both the V14 peptide and the sialidase inhibitor 2-deoxy-2,3-didehydro-N-acetylneuraminic acid (DANA). These results demonstrate, for the first time, that binding of EDP to the ERC indirectly modulates CD36 sialylation level and regulates oxidized LDL uptake through this sialidase. These effects could contribute to the previously reported proatherogenic role of EDP and add a new dimension in the regulation of biological processes through NEU1