Behavior of glycolylated sialoglycans in the binding pockets of murine and human CD22

Carluccio, Cristina Di; Forgione, Rosa Ester; Montefiori, Marco; Civera, Monica; Sattin, Sara; Smaldone, Giovanni; Fukase, Koichi; Manabe, Yoshiyuki; Crocker, Paul R.; Molinaro, Antonio; Marchetti, Roberta; Silipo, Alba

doi:10.1016/j.isci.2020.101998

Cited by 10 publications

(7 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although the orientation around the Neu5Ac-α-(2-6)-Gal was the same as observed for natural CD22 ligands [7][8]34] also when interacting with other Siglecs, as Siglec-10, [35] our results suggested a more extended conformation of the analogue 1 if compared to the natural ligand due to the presence of the rigid aglycon moiety. Moreover, docking and modelling studies provided insights into the fine structural characteristics of the interacting interfaces.…”

Section: Discussionsupporting

confidence: 68%

Conformationally Constrained Sialyl Analogues as New Potential Binders of h‐CD22

et al. 2022

Self Cite

View full text Add to dashboard Cite

Here, two conformationally constrained sialyl analogues were synthesized and characterized in their interaction with the inhibitory Siglec, human CD22 (h-CD22). An orthogonal approach, including biophysical assays (SPR and fluorescence), ligand-based NMR techniques, and molecular modelling, was employed to disentangle the interaction mechanisms at a molecular level. The results showed that the Sialyl-TnThr antigen analogue represents a promising scaffold for the design of novel h-CD22 inhibitors. Our findings also suggest that the introduction of a biphenyl moiety at position 9 of the sialic acid hampers canonical accommodation of the ligand in the protein binding pocket, even though the affinity with respect to the natural ligand is increased. Our results address the search for novel modifications of the Neu5Ac-α(2-6)-Gal epitope, outline new insights for the design and synthesis of high-affinity h-CD22 ligands, and offer novel prospects for therapeutic intervention to prevent autoimmune diseases and B-cell malignancies.

show abstract

Section: Discussionsupporting

confidence: 68%

Conformationally Constrained Sialyl Analogues as New Potential Binders of h‐CD22

et al. 2022

Self Cite

View full text Add to dashboard Cite

show abstract

“…CD22 recognizes only the terminal disaccharide portions of the N -glycan, regardless of the branch to which they are attached, and reveals that the binding mode to CD22 is superficial and not influenced by the internal sugar residues of the N -glycan. The interaction of Neu5Gc derived ligands with CD22 was also investigated ( Di Carluccio et al, 2021 ) and demonstrated that the Neu5Gc ligand exhibits a similar binding epitope and orientation to CD22 than the Neu5Ac counterpart.…”

Section: Sialic Acid—siglec Interactionsmentioning

confidence: 99%

Molecular Recognition Insights of Sialic Acid Glycans by Distinct Receptors Unveiled by NMR and Molecular Modeling

Soares

Grosso

Ereño‐Orbea

et al. 2021

Front. Mol. Biosci.

View full text Add to dashboard Cite

All cells are decorated with a highly dense and complex structure of glycan chains, which are mostly attached to proteins and lipids. In this context, sialic acids are a family of nine-carbon acidic monosaccharides typically found at the terminal position of glycan chains, modulating several physiological and pathological processes. Sialic acids have many structural and modulatory roles due to their negative charge and hydrophilicity. In addition, the recognition of sialic acid glycans by mammalian cell lectins, such as siglecs, has been described as an important immunological checkpoint. Furthermore, sialic acid glycans also play a pivotal role in host–pathogen interactions. Various pathogen receptors exposed on the surface of viruses and bacteria are responsible for the binding to sialic acid sugars located on the surface of host cells, becoming a critical point of contact in the infection process. Understanding the molecular mechanism of sialic acid glycans recognition by sialic acid-binding proteins, present on the surface of pathogens or human cells, is essential to realize the biological mechanism of these events and paves the way for the rational development of strategies to modulate sialic acid-protein interactions in diseases. In this perspective, nuclear magnetic resonance (NMR) spectroscopy, assisted with molecular modeling protocols, is a versatile and powerful technique to investigate the structural and dynamic aspects of glycoconjugates and their interactions in solution at the atomic level. NMR provides the corresponding ligand and protein epitopes, essential for designing and developing potential glycan-based therapies. In this review, we critically discuss the current state of knowledge about the structural features behind the molecular recognition of sialic acid glycans by different receptors, naturally present on human cells or pathogens, disclosed by NMR spectroscopy and molecular modeling protocols.

show abstract

“…The anomeric positions were chosen based on lectin crystallography studies and biological data suggesting that this site would be the most inert position for derivatization. [31][32][33] With probes in hand, we evaluated their engagement with plant lectins in vitro. Plant lectins, such as LTL, MAL II, and SNA, are commonly used reagents to describe glycan patterns in cells.…”

Section: Resultsmentioning

confidence: 99%

Chemoproteomic mapping of human milk oligosaccharide (HMO) interactions in cells

et al. 2022

View full text Add to dashboard Cite

show abstract

Behavior of glycolylated sialoglycans in the binding pockets of murine and human CD22

Cited by 10 publications

References 35 publications

Conformationally Constrained Sialyl Analogues as New Potential Binders of h‐CD22

Conformationally Constrained Sialyl Analogues as New Potential Binders of h‐CD22

Molecular Recognition Insights of Sialic Acid Glycans by Distinct Receptors Unveiled by NMR and Molecular Modeling

Chemoproteomic mapping of human milk oligosaccharide (HMO) interactions in cells

Contact Info

Product

Resources

About