Crystal structures of the peanut lectin in the presence of novel β-S- and β-N-galactosides

SEBASTIÁN KLINKE; MARIÑO, KARINA V.; OTERO LISANDRO; ALEJANDRO J. CAGNONI; WALTER GIORDANO; MARÍA LAURA UHRIG; EMILIANO PRIMO; CANO, MARÍA EMILIA; GOLDBAUM, F. A.

Buenos Aires

Congreso; GlycoAr 2019; 2019

Sociedad Argentina de Glicobiología

Carbohydrate−protein interactions are involved in important cellular recognition processes, including viral and bacterial infections, inflammation, and tumor metastasis. Hence, glycoclusters that interfere with sugar−protein recognition processes are seen as promising chemotherapeutics. Legume lectins are excellent models for the study of the recognition process. Among them, the peanut lectin (PNA) is very relevant in the glycobiology field, because of its specificity for β-galactosides, showing high affinity towards Thomsen-Friedenreich (TF) antigen, a well-known tumor-associated carbohydrate antigen. Thus, the design and synthesis of high affinity multivalent ligands of 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 PNA in complex with novel synthetic hydrolytically stable β-S- and β-N-galactosides. The complexes reveal key molecular binding interactions of different sugars to PNA at the atomic level. Furthermore, binding affinity studies measured by isothermal titration calorimetry (ITC) showed dissociation constant (Kd) 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.