Carbohydrate-lectin interactions play an important role in the immune system with functions including cell adhesion, glycoprotein turnover and recognition and neutralization of pathogen e.g. by triggering immune responses. Although carbohydrate-lectin interactions are highly specific, their binding strength is relatively weak; binding affinity can be increased by a multivalent ligand presentation or chem. optimizing ligands to the lectin binding site. Carbohydrate microarrays have recently emerged as high-throughput tools for studying carbohydrate-protein interactions and for screening the specificity of carbohydrate processing enzymes. Here, we present a combination of enzymic synthesis on printed glycan scaffolds with subsequent chem. diversification for the on-chip prepn. of a large collection of glycomimetics for screening of C-type lectin ligands with increased affinity. Our glycan array platform with glycans hydrophobically attached to a transparent and conductive indium tin-oxide coated glass slide allows the in situ anal. of chem. and enzymic transformations by mass spectrometry while interactions with labeled proteins can be obsd. with a fluorescence scanner. Initially a no. of N-glycan scaffolds with varying antennae no. are immobilized on the surface; subsequently, by enzymic elongation with a mutant galactosyl transferase and non-natural azido-N-acetyl-D-galactosamine nucleotide donor, one or more azides were introduced on all substrates on the chip. The azide functions were then reacted with a panel of structurally and electronically varied alkynes by copper(I)-catalyzed azido alkyne cycloaddn. (CuAAC) to arrive at a library of N- glycan mimetics with novel binding properties compared to the natural homologues.
On chip development of N-glycan mimetics for improving CLRs targeting / A. Cioce, S. Serna, A. Hernandez, G. Goti, A. Bernardi, N.C. Reichardt. ((Intervento presentato al 28. convegno International Carbohydrate Symposium tenutosi a New Orleans nel 2016.
|Titolo:||On chip development of N-glycan mimetics for improving CLRs targeting|
|Data di pubblicazione:||lug-2016|
|Settore Scientifico Disciplinare:||Settore CHIM/06 - Chimica Organica|
|Citazione:||On chip development of N-glycan mimetics for improving CLRs targeting / A. Cioce, S. Serna, A. Hernandez, G. Goti, A. Bernardi, N.C. Reichardt. ((Intervento presentato al 28. convegno International Carbohydrate Symposium tenutosi a New Orleans nel 2016.|
|Appare nelle tipologie:||14 - Intervento a convegno non pubblicato|