Biology subjects

Vos, G. M.

Publications and source records attributed to Vos, G. M..

3 recordsLinked to original sources

bioRxiv2026

Chemoenzymatic Synthesis of 6-Sulfo Sialyl Lewisx Containing Glycans to Probe the Receptor Specificity of MERS Coronavirus

The initial attachment of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) to host cell sialosides is critical for infection, yet its precise receptor specificity remains poorly understood. Here, we describe a chemoenzymatic methodology to synthesize a comprehensive panel of 6-sulfo sialyl Lewisx (6-sulfo-SLex) containing glycans. Our approach entails the enzymatic assembly of an oligo-lactosamine chain modified at specific positions with N-trifluoroacetyl-glucosamine (GlcNTFA) moieties. Mild base treatment removes the TFA group to yield glucosamine, which effectively blocks enzymatic fucosylation. By leveraging this approach alongside the unique substrate selectivity of GlcNAc-6-O-sulfotransferases 2 (CHST-2), we achieved the selective preparation of fucosylated 6-sulfo-SLex glycans. Microarray screening of these printed glycans revealed that a 6-sulfo-SLex derivative presented on an extended LacNAc chain is the preferred host receptor for MERS-CoV. Conjugation of this lead compound to a polyglycerol-based dendrimer generated a multivalent inhibitor that potently blocks hemagglutination of human red blood cells by the MERS-CoV spike protein N-terminal domain (NTD). Furthermore, computational modeling demonstrated that the fucose moiety does not directly contact the viral spike protein. Instead, it pre-organizes the ligand into a favorable conformation, enabling a critical salt bridge between the glycans sulfate group and the guanidinium side chain of viral residue Arg307.

biochemistry↗

bioRxiv2026

Glycosaminoglycans Promote Amyloid-β Aggregation via Multivalent, pH-Dependent Interactions

Glycosaminoglycans (GAGs) are polyanionic polysaccharides that co-localize with amyloid-{beta} (A{beta}) deposits in Alzheimers disease, yet their mechanistic contribution to A{beta} aggregation remains unclear. Here, we show that GAGs function as pH-responsive electrostatic scaffolds that selectively accelerate A{beta}(1-42) aggregation under mildly acidic, endosomal conditions but not at neutral extracellular pH. Combining experimental and computational approaches, we identify protonated N-terminal histidines as key determinants of GAG binding. Weak interactions between GAGs and the charged Nterminal region of A{beta} promote conformational rearrangements that bring peptides into proximity and expose adjacent hydrophobic aggregation-prone segments, thereby facilitating peptide clustering. Kinetic analyses reveal that aggregation is enhanced in a way consistent with an apparent increase in effective peptide concentration, accelerating nucleation without altering the dominant aggregation pathway. Systematic variation of GAG chain length and sulfation level further demonstrates that aggregation enhancement requires a threshold degree of multivalency, consistent with a clustering-driven mechanism. Together, these findings establish a framework in which pH-dependent electrostatic interactions with GAGs act as molecular triggers of amyloid nucleation, providing insight into how cellular microenvironments regulate the earliest stages of Alzheimers disease pathology.

biophysics↗

bioRxiv2025

De novo sequencing of complex glycans by ion mobility-mass spectrometry using a self-expanding reference database

It is essential to determine exact structures of glycans in complex biological samples to understand their biology and exploit their diagnostics, therapeutics and nutraceuticals potential. An unresolved analytical challenge is the identification of isomeric glycan structures in complex biological samples. Ion mobility (IM) combined with MS enables separation of isomeric glycans and identification by comparing their intrinsic collision cross section (CCS) values with similar data of synthetic standards. To identify glycans without the need to synthesize all biologically occurring glycans, we describe here an IM-MS de novo sequencing method based on fragment identification and sequence assembly. CCS values of additional fragments from glycans in biological samples resulted in a self-expanding reference database, gradually facilitating the sequencing of glycans of increasing complexity and expanding the database from an initial 20 standards to 332 unique entries. The methodology was employed to determine exact structures of human milk oligosaccharides and N-glycans of biotherapeutics.

biochemistry↗