Glycodendritic structures: tools to interact with DC-SIGN

The key role of carbohydrates in many biological events has attracted the interest of the scientific community. This fact has demanded the access to new tools necessary to understand this role and the interaction of carbohydrates with their corresponding receptors, lectins. Glycodendrimers and glycodendritic structures in general, have demonstrated to be very efficient and interesting tools to intervene in those processes where carbohydrates participate. In this review, we discuss the different glycodendritic structures that have been used to interfere with DC-SIGN, a very attractive lectin involved in infection processes and in the regulation of the immune response.

O papel chave dos carboidratos em muitos eventos biológicos tem atraído interesse da comunidade científica. Este fato demonstrou o acesso de novas ferramentas para a compreensão da interação dos carboidratos com seus receptores correspondentes, lectinas. Glicodendrímeros e estruturas glicodendríticas, em geral, mostram-se como ferramentas muito eficientes e interessantes para intervir nos processos em que os carboidratos participam. Nesta revisão, discutimos diferentes estruturas glicodendríticas que têm sido úteis para interferir com DC-SIGN, uma lectina muito atraente envolvida em processos infecciosos e na regulação da resposta imune.

Kinetics of translation and glycosylation of pituitary glycoproteins

The present study determines the basal kinectics of synthesis of translation (by[(14)C] leucine incorporation. [(14)C] leu-PROT] and of proximal (by [(3)H] mannose incorparation. [(3)H] man-PROT) and distal (by [3H] galactose incorporation, [(3)H] gal-PROT) glycosylation of total adenohypophyseal glycoproteins, by rat pituitary cells in primary culture. In order to obtain more information regarding the role of both septs of glycosylation on the secretory process, the effects of cycloheximide (CH; translation inhibitor) and tunicamycin (TM; glycosylation inhibitor) on the kinetics of synthesis and release of pituitary glycoproteins were also studied. Cells were incubated in medium containing [(14)C] leu plus [(3)H] man or [(14)C] leu plus [(3)H] gal, for various time-intervals (from 0.5 to 5h) in the abscence (control) or presence of different doses od CH (1.0;4.0 or 16.0 mug/ml) or TM (0.5;1.0 or 2.0 mug/ml). The kinetics of synthesis (slope=3488) and release (slope=622) of [(14)C] le-PROT were higler than those of the sugar percursos (slopes: [(3)H] man-PROT=1751 and 526; [(3)H] gal-PROT=1231 and 506). Leucine or mannose-labeled protein was barely detectable in the medium after 2h incubation, whereas galactose-labeled protein had already been released into the incubation medium by 30min. Cycloheximide induced translation blockage and, concomitantly, produced a marked inhibition of [(3)H] man incorporation. On the other hand, TM inhibited the kinetics of synthesis and release of [(3)H] man-PROT without affecting those of [(14)C] leu-PROT. The kinetics of synthesis and release of [(3)H] gal-PROT, although diminished, maintained linearity and increased in function of time, even in the presence of the antibiotics. Thus, the present results on glycoproteins from the pituitary gland are consistent with the previous conclusion for other mammalian glycoproteins that carbohydrate attachment occurs in several steps to molecules destined to be secreted. Addition of mannose (proximal glycosylation) is a co-translational event and that of galactose (distal glycosylation) is post-translational and can be designated as final stages in carbohydrate assembly, occurring close to the time of release. Furthermore, it has been demonstrated that the absence of the carbohydrate side chains of the pituitary glycoprotein does not prevent the intracellular transport of the protein and its export from the cell.