Orthogonal photoswitching of heterobivalent azobenzene glycoclusters: the effect of glycoligand orientation in bacterial adhesion

Beilstein Journal of Organic Chemistry, Год журнала: 2025, Номер 21, С. 736 - 748

Опубликована: Апрель 8, 2025

Carbohydrate recognition is fundamental to a plethora of cellular processes and hence the elucidation structural determinants process prerequisite for understanding manipulating carbohydrate-protein interactions, such as in inhibition carbohydrate-specific bacterial adhesion. For receptor binding, glycoligands have be properly oriented three-dimensional space additionally, secondary interactions exerted by multivalent an effect on affinity. A recently introduced orthogonally photoswitchable heterobivalent azobenzene Glc/Man glycocluster was utilized examine these aspects carbohydrate adhesion-inhibition assay. The measured results were systematically contextualized employing new reference compounds respective homobivalent Man/Man glycocluster. An in-depth study comprising analysis photochromic properties potential inhibitors adhesion synthetic glycophotoswitches their different isomeric states led insights into role ligand orientation recognition. experimental underpinned molecular modeling.

Язык: Английский

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Bioactive Polymeric Scaffolds: Multivalent Functionalization by Thermal Azide–Alkyne Cycloaddition with Alkynyl Dicarbamates

Biomacromolecules, Год журнала: 2025, Номер unknown

Опубликована: Март 26, 2025

Multivalency enables interactions with higher affinities and specificities than monovalent interactions. The strategy exploited by nature to modulate biorecognition has inspired the design of multivalent conjugates therapeutic properties. However, chemical functionalization often requires coupling agents, additives, or metal catalysts that complicate isolation purification. Herein, azide–alkyne cycloaddition (AAC) alkynyl dicarbamates (Alk-R) is presented as a flexible, reliable, atom-economical, user-friendly for polymeric scaffolds. Alk-R functionalized biologically relevant ligands have been prepared used AAC azide-bearing dendrimers block copolymers. resulting polymers double multivalency reveal platform development bioinspired functional systems promising applications in drug delivery: copolymer micelles multifunctional nanocarriers synergistically integrated probes-ligands-drugs. extension this other scaffolds expected open up wide range diagnostic opportunities.

Язык: Английский

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Chemoenzymatic synthesis of sialylated and fucosylated mucin analogs reveals glycan-dependent effects on protein conformation and degradation

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Апрель 17, 2025

Abstract Mucin proteins are essential for life but challenging to study due their complex glycosylation patterns. Synthetic mimics have become vital tools understanding and modulating the roles of mucins in human health disease. We developed a chemoenzymatic approach prepare polypeptide-based synthetic displaying variety glycans with native linkages orientations. By combining polymerization glycosylated amino acid N -carboxyanhydrides enzymatic sialylation fucosylation, we produced tunable panel mucins. These polymers were recognized by natural glycan-binding glycan-degrading enzymes, providing insights into structural preferences these proteins. Glycan- linkage-dependent effects on proteolysis observed. Further, investigation influence peptide backbone secondary structure revealed that both linkage at Ser vs. Thr profound hierarchical conformation. Overall, our methodology offers versatile exploring diverse glycobiology

Язык: Английский

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Comparative anatomy of siphophage tails before and after interaction with their receptor

Current Opinion in Structural Biology, Год журнала: 2025, Номер 92, С. 103045 - 103045

Опубликована: Апрель 24, 2025

Язык: Английский

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Overcoming the novel glycan-lectin checkpoints in tumor microenvironment for the success of the cross-presentation-based immunotherapy

Biomaterials Science, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

(a) Two primary mechanisms for cross-presentation of internalized antigens: cytosolic and vacuolar pathways. (b) To enhance antigen presentation generate T cell responses, glycans are multivalently presented on a range nanocarrier systems.

Язык: Английский

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Multivalent Siglec Ligands

Carbohydrate Research, Год журнала: 2025, Номер unknown, С. 109520 - 109520

Опубликована: Май 1, 2025

Язык: Английский

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Exploring Multivalent Architectures for Binding and Stabilization of N-Acetylgalactosamine 6-Sulfatase

Molecules, Год журнала: 2025, Номер 30(10), С. 2222 - 2222

Опубликована: Май 20, 2025

Morquio A syndrome is a lysosomal disorder caused by the deficiency of enzyme N-acetylgalactosamine 6-sulfatase (GALNS, EC 3.1.6.4). Currently, replacement therapy (ERT) used to treat through infusion recombinant VIMIZIM® (elosulfase alfa, BioMarin). Unfortunately, exhibits low conformational stability in vivo. promising approach address this issue coadministration human GALNS (rhGALNS) with pharmacological chaperone (PC), molecule that selectively binds misfolded protein, stabilizes its conformation, and assists restoration impaired function. We report work synthesis library multivalent glycomimetics exploiting copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction between several dendrimeric scaffolds armed terminal alkynes azido ending iminosugars different structures (pyrrolidines, piperidines, pyrrolizidines) or simple carbohydrates as bioactive units. The biological evaluation identified pyrrolidine-based nonavalent dendrimers 1 36 most compounds, able both bind native IC50 micromolar range act stabilizers toward rhGALNS thermal denaturation study, thus identifying compounds for combined PC/ERT therapy.

Язык: Английский

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Roles for Siglec-glycan interactions in regulating immune cells

Seminars in Immunology, Год журнала: 2024, Номер 77, С. 101925 - 101925

Опубликована: Дек. 19, 2024

Язык: Английский

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Multivalent GCase Enhancers: Synthesis and Evaluation of Glyco-Gold Nanoparticles Decorated with Trihydroxypiperidine Iminosugars

Bioconjugate Chemistry, Год журнала: 2024, Номер unknown

Опубликована: Дек. 19, 2024

The present study reports the preparation of first multivalent iminosugars built onto a glyco-gold nanoparticle core (glyco-AuNPs) capable stabilizing or enhancing activity lysosomal enzyme GCase, which is defective in Gaucher disease. An N-nonyltrihydroxypiperidine was selected as bioactive iminosugar unit and further functionalized, via copper-catalyzed alkyne–azide cycloaddition, with thiol-ending linker that allowed conjugation to gold core. These ligands were obtained either linear monomeric dendritic trimeric arrangement iminosugar. concentration on surface modulated different amounts glucoside bearing short spacer inner ligand. new mixed-ligand coated glyco-AuNPs fully characterized, those highest colloidal stability aqueous medium subjected biological evaluation. Glyco-AuNPs units showed ability stabilize recombinant GCase thermal denaturation assay, while able enhance mutant patient's fibroblasts by 1.9-fold at 2.2 μM.

Язык: Английский

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Multifunctional Theranostic Glyconanoprobes for Synergistic Eradication of Breast Cancer

Journal of Materials Chemistry B, Год журнала: 2024, Номер unknown

Опубликована: Дек. 24, 2024

The development of multifunctional theranostic glyconanoprobes for breast cancer is distinguished by their tumor-targeting capability and enhanced antitumor efficacy, achieved through synergistic chemo-gene photothermal therapy.

Язык: Английский

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