Rational Design of Highly Selective Sialyllactose‐Imprinted Nanogels

• Published in: Chemistry : a European journal 2024-08, Vol.30 (45), p.e202401232-n/a
• Main Authors: Contardi, Cecilia, Mavliutova, Liliia, Serra, Massimo, Rubes, Davide, Dorati, Rossella, Vistoli, Giulio, Macorano, Alessio, Sellergren, Börje, De Lorenzi, Ersilia
• Format: Article
• Language: English
• Subjects: Affinity; Affinity capillary electrophoresis; Boronic acid derivatives; Capillary electrophoresis; Carbohydrates; Chemical synthesis; Electrophoresis; Electrophoretic mobility; Glycosylation; Imprinted polymers; Molecular imprinting; Monomers; Nanogels; NMR; Nuclear magnetic resonance; Polymers; Polysaccharides
• ISSN: 0947-6539; 1521-3765; 1521-3765
• DOI: 10.1002/chem.202401232

We describe a facile method to prepare water‐compatible molecularly imprinted polymer nanogels (MIP NGs) as synthetic antibodies against target glycans. Three different phenylboronic acid (PBA) derivatives were explored as monomers for the synthesis of MIP NGs targeting either α2,6‐ or α2,3‐sialyllactose, taken as oversimplified models of cancer‐related sT and sTn antigens. Starting from commercially available 3‐acrylamidophenylboronic acid, also its 2‐substituted isomer and the 5‐acrylamido‐2‐hydroxymethyl cyclic PBA monoester derivative were initially evaluated by NMR studies. Then, a small library of MIP NGs imprinted with the α2,6‐linked template was synthesized and tested by mobility shift Affinity Capillary Electrophoresis (msACE), to rapidly assess an affinity ranking. Finally, the best monomer 2‐acrylamido PBA was selected for the synthesis of polymers targeting both sialyllactoses. The resulting MIP NGs display an affinity constant≈106 M−1 and selectivity towards imprinted glycans. This general procedure could be applied to any non‐modified carbohydrate template possessing a reducing end. Three different monomers were explored for the synthesis of imprinted nanogels targeting α2,6‐ or α2,3‐sialyllactose, taken as oversimplified models of cancer‐related sT and sTn antigens. A bottom‐up platform including NMR spectroscopy, ARS titration, in silico studies and Affinity Capillary Electrophoresis provides a ranking and leads to the best material in terms of affinity and selectivity.