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

KLINKE, SEBASTIÁN; MARIÑO, KARINA; OTERO, LISANDRO H.; CAGNONI, ALEJANDRO J.; GIORDANO, WALTER; UHRIG, MARIA L.; PRIMO, EMILIANO D.; CANO, MARIA E.; GOLDBAUM, FERNANDO A.

Buenos Aires

Simposio; 3rd Argentinian Symposium on Glycobiology; 2019

Universidad Nacional de San Martin

Carbohydrate-proteininteractions are involved in important cellular recognitionprocesses, including viral and bacterialinfections, inflammation, and tumor metastasis. Hence, glycoclustersthat interfere with these processesare seen as promising chemotherapeutics. Plant lectins are excellentmodels to explore the recognitionfeatures involved. Among them, the peanut lectin (PNA) is veryrelevant in the glycobiology field, becauseof its specificity for β-galactosides, showing high affinity towardsThomsen-Friedenreich (TF) antigen, a well-knowntumor-associated carbohydrate antigen. Given this specificity, thePNA lectin is one of the most potentialmolecular probes available for the recognition of tumor cellO-glycans, thus, it has been extensively usedin the glycobiology field on inhibition studies, including our own,of a variety of β-galactoside and β-lactosideligands. The design and synthesis of high affinity multivalentligands for PNA has been actively pursued over the last years. Aspart of our ongoing research project on synthetic glycomimetics asligands of lectins, we report here the crystalstructures of PNA incomplex with novel synthetic β-S- and β-N-galactosides. Thecomplexes reveal key molecular binding interactions of differentsugars to PNA at the atomic level. Furthermore, binding affinitystudies measured by isothermal titration calorimetry (ITC) showeddissociation constant (K d ) values in the micromolar range, as wellas a positive effect in terms of the affinity in the case of thedivalent compounds. Taken together, these results providequalitative structural rationale for the upcoming synthesis ofoptimized glycoclusters, designed to interfere inlectin-mediated biological processes, in the search of high affinitymultivalent ligands of lectins, a field that has beenextensively explored during the last years.