Crystal structures of the peanut lectin in the presence of novel beta-S- and beta-N-galactosides (Póster)

EMILIANO PRIMO; MARÍA E. CANO; FERNANDO A. GOLDBAUM; SEBASTIÁN KLINKE; KARINA V. MARIÑO; LISANDRO OTERO; ALEJANDRO J. CAGNONI; WALTER GIORDANO; MARÍA L. UHRIG

San Martín, Pcia. de Buenos Aires

Simposio; III Simposio Argentino de Glicobiología GlycoAR2019; 2019

Universidad Nacional de San Martín

Carbohydrate-protein interactions are involved in cellular recognition processes that include viral and bacterial infections, inflammation, and tumor metastasis. Hence, glycoclusters that interfere with sugar-protein recognition processes are seen as promising chemotherapeutics. Legume lectins provide excellent models for the study of the recognition process. Among them, peanut lectin (PNA) is very relevant in the glycobiology field, because of its specificity for beta-galactosides, showing high affinity towards N-acetyllactosamine and Thomsen-Friedenreich (TF) antigen, a well-known tumor-associated carbohydrate antigen. Thus, the design and synthesis of high affinity multivalent ligands on PNA has been actively pursued over the last years. As part of our ongoing research project on the characterization of multivalent ligands with modified glycosidic bonds, we report here the crystal structures of the complex of PNA with novel synthetic hydrolytically stable beta-S- and beta-N-galactosides. The complexes reveal key molecular interactions of binding of different sugars to PNA at the atomic level. Furthermore, binding affinity studies, measured by isothermal titration calorimetry (ITC), showed association constant (Ka) values in the micromolar range as well as a multivalent effect. Taken together, these results provide qualitative structural rationale for the upcoming synthesis of optimized glycoclusters, designed to interfere in lectin-mediated biological processes.