Selectively Charged and Zwitterionic Analogues of the Smallest Immunogenic Structure of Streptococcus Pneumoniae Type 14

Abstract

Zwitterionic polysaccharides (ZPs) have been shown in recent years to display peculiar immunological properties, thus attracting the interest of the carbohydrate research community. To fully elucidate the mechanisms underlying these properties and exploit the potential of this kind of structures, in depth studies are still required. In this context, the preparation of two cationic, an anionic, as well as two zwitterionic tetrasaccharide analogues of the smallest immunogenic structure of Streptococcus pneumoniae type 14 (SP14) capsular polysaccharide are presented. By exploiting a block strategy, the negative charge has been installed on the non-reducing end of the lactose unit of the tetrasaccharide and the positive charge either on the non-reducing end of the lactosamine moiety or on an external linker. These structures have then been tested by competitive ELISA, showing that the structural variations we made do not modify the affinity of the neutral compound to binding to a specific antibody. However, lower efficacies than the natural SP14 compound were observed. The results obtained, although promising, point to the need to further elongate the polysaccharide structure, which is likely too short to cover the entire epitopes.

Developments in Carbohydrate-Based Metzincin Inhibitors

“…Nowadays, it is well known how a wide range of glycosylated derivatives such as glycoproteins or glycosylated natural products, are crucial for physiological [ 57 ] and pathological processes [ 58 ]. Particularly interesting is the protein-carbohydrate recognition, a phenomenon fundamental in many cellular mechanisms, such as migration, adhesion, cell-differentiation, tumor progression, infections (by viruses or bacteria), and immune response among others [ 59 , 60 , 61 , 62 , 63 ]. In the last years, the ubiquity but also the biological properties of glycoproteins or glycosylated natural products have driven research towards the synthesis of glycoconjugates for the development of drug candidates with anti-infectious, anti-inflammatory, anticancer, or vaccine activity [ 64 , 65 , 66 ].…”