Multivalent α-Gal neoglycoconjugate for immunological studies in Chagas Disease

MARINO C.; GIORGI, M. E.; LEDERKREMER R. M.

Lisboa

Simposio; 29º International Carbohydrates Symposium; 2018

ICO

Synthetic oligosaccharides and their glycoconjugates are useful tools for the diagnostic of several diseases and for immunological studies. On the other hand, the introduction of multivalency by incorporation of an antigenic structure into a multiarm scaffold increases the density of the epitopes, similarly to the presentation that glycoconjugates often have in biological systems. This increment favors the binding specificity to serum antibodies.Carbohydrate PEGylation using poly(ethylene glycol) (PEG) scaffolds have been used for many application in chemotherapy and drug delivery to prolong the in vivo circulation half-life, and to enhance the solubility and stability of conjugates.[1,2] We have previously proved that lactose analogs, inhibitors of trans-sialidase from Trypanosoma cruzi, linked to a multi ARM PEG improved their bioavailability retaining the inhibitory properties.[3] Herein we describe a straightforward synthesis of disaccharide 6-aminohexyl α-D-Galp(1→3)β-D-Galp, which is the minimal antigenic unit present in trypomastigote mucins of chronic chagasic patients, and its conjugation via an amino coupling with N-hydroxysuccinimide activated octa-ARM PEG platform (NHS 8-ARM PEG, MW 40000). In this way an octavalent homogeneous PEG-derivative with high molecular weight containing 8 units of the synthetic carbohydrate antigen was afforded. The substitution of all the arms was confirmed by analysis of the NMR spectra. This multivalent neoglycoconjugate is a good candidate for immunological studies