Serine versus Threonine Glycosylation with α‐O‐GalNAc: Unexpected Selectivity in Their Molecular Recognition with Lectins

Abstract

The molecular recognition of several glycopeptides bearing Tn antigen (α-O-GalNAc-Ser or α-O-GalNAc-Thr) in their structure by three lectins with affinity for this determinant has been analysed. The work yields remarkable results in terms of epitope recognition, showing that the underlying amino acid of Tn (serine or threonine) plays a key role in the molecular recognition. In fact, while Soybean agglutinin and Vicia villosa agglutinin lectins prefer Tn-threonine, Helix pomatia agglutinin shows a higher affinity for the glycopeptides carrying Tn-serine. The different conformational behaviour of the two Tn biological entities, the residues of the studied glycopeptides in the close proximity to the Tn antigen and the topology of the binding site of the lectins are at the origin of these differences.

Detection of Tumor-Associated Glycopeptides by Lectins: The Peptide Context Modulates Carbohydrate Recognition

“…In fact, our preliminary studies with glycine-rich glycopeptides bearing Tn antigen indicate a clear decrease of affinity with SBA lectin. 20 To rationalize these experimental findings, and considering the similar results found for the short (1−3) and large glycopeptides (m1−m3), we performed a thorough conformational analysis in solution of glycopeptides 1−3 in both the free and bound states with SBA lectin. First, full assignment of the protons of the three compounds was performed using COSY and HSQC experiments (Supporting Information).…”

Structural Insights into the Binding of Sugar Receptors (Lectins) to a Synthetic Tricyclic Tn Mimetic and Its Glycopeptide Version

“…HPA is an animal lectin, from edible snail, that has been used to explore the expression of Tn and Tn‐related antigens on cancer cells 20. It binds Forssman and histo‐blood group A antigens, thus GalNAc in the α‐anomeric form,14 and shows selectivity for glycopeptides carrying Tn‐serine over Tn‐threonine 21. The contact pattern with GalNAc/α‐GalNAc‐Ser is very close, with van der Waals interactions at C‐1 (with His84) and C‐6 (with Tyr89), and eight hydrogen bonds involving the oxygen atoms at C‐2–C‐6 14a,20a…”

Recent advances in methods for the analysis of protein o‐glycosylation at proteome level

“…Lectin is a type of proteins that can recognize certain type of sugar chains linked to proteins. Different kinds of lectins have different specificities to not only the sugar chain structure but also the surrounding amino acid sequences . The lectin‐enriched O‐GalNAc peptides are subjected to MS detection for characterization.…”