Síntese de glicodendrímeros e avaliação de sua interação com lectinas

Abstract

The Cell surface is composed of proteins, lipides and carbohydrates. The carbohydrates of cell surface are conjugated with proteins and lipids, forming glycoproteins or glycolopides. These macromolecular glycoconjugates interact with proteins named lectins in a specific way. Seeds of ERYTHRINA CRISTAGALLI L. (Fabaceae) have a lectin which interacts specifically with D- galactose and N- acetil-lactosamine. Many lectins are involved in the recognition of the carbohydrates present in the cell surface of invasive microorganisms. On the other hand, many microorganisms have evolved strategies to explore these recognition processes and use it to invade cells of the immune system. Some studies have proposed that the Human Immunodeficiency Virus (HIV), assumed as the etiologic agent of the acquired Immunodeficiency Syndrome (AIDS), interacts with the DC-SIGN (dendrict cell-specific ICAM-3-grabbing non-integrin) lectin to be transported to the lymphoid sites. This lectin recognize D- mannose and L-fucose by multivalence. DC-SIGN is an important target to the anti-adhesins, a class of substances with block the interaction between oligossacharides and lectins, since they can mimic these membrane constituents. Glycodendrimers are anti-adhesins molecules. In this work are described the syntheses of monomeric, dimeric and tetrameric D- galactose derivates designed as anti-adhesins. It´s also described the synthesis of monomeric and tetrameric D-manose and D-glucose by alternative methods. From the derivates obtained by synthesis, two monomers (n-(2-hydroxyethyl)-4-(b-d galactopyranosyloxy) benzenepropanamide and N-(2- hydroxieth)- 4-(b-d galactopyranosyloxy) -3-ethoxybenzenepropanamide) and two dimmers (N,N-bis-{4-B-D- galactopyranosyloxy)benzenepropanoyl]-1,4- butanediamine and N,N-bis-[3-(4-B-D-galactopyranosyloxi-3-methoxyphenyl)propanoyl}-1-4-butanediamine) were evaluated as inhibitors of the hemmaglutination process mediated by the lectin of Erythrina cristagalli. The interaction between the tetramer pentaerythrityl tetra [3-[[[1-(4-methylphenyl)-6-deox-alfa-D-MANNOPYRANOSID-6-YL]amino]carbonyl]propanoate] and the lectin D-SIGN were evaluated by surface Plasmon resonance.