Glyco-gold nanoparticles: Synthesis and applications

Glyco-gold nanoparticles combine in a single entity the peculiar properties of gold nanoparticles with the biological activity of carbohydrates. The result is an exciting nanosystem, able to mimic the natural multivalent presentation of saccharide moieties and to exploit the peculiar optical properties of the metallic core. In this review, we present recent advances on glyco-gold nanoparticle applications in different biological fields, highlighting the key parameters which inspire the glyco nanoparticle design

Synthesis and biological evaluation of a trisaccharide repeating unit derivative of Streptococcus pneumoniae 19A capsular polysaccharide

Streptococcus pneumoniae (SP) is a common human pathogen associated with a broad spectrum of diseases and it is still a leading cause of mortality and morbidity worldwide, especially in children. Moreover, SP is increasingly associated with drug resistance. Vaccination against the pathogen may thus represent an important strategy to overcome its threats to human health. In this context, revealing the molecular determinants of SP immunoreactivity may be relevant for the development of novel molecules with therapeutic perspectives as vaccine components. Serogroup 19 comprises the immune-cross reactive types 19F, 19A, 19B and 19C and it accounts for a high percentage of invasive pneumococcal diseases, mainly caused by serotypes 19F and 19A. Herein, we report the synthesis and biological evaluation of an aminopropyl derivative of the trisaccharide repeating unit of SP 19A. We compare two different synthetic strategies, based on different disconnections between the three monosaccharides which make up the final trisaccharide, to define the best approach for the preparation of the trisaccharide. Synthetic accessibility to the trisaccharide repeating unit lays the basis for the development of more complex biopolymer as well as saccharide conjugates. We also evaluate the binding affinity of the trisaccharide for anti-19A and anti-19F sera and discuss the relationship between the chemical properties of the trisaccharide unit and biological activity

Exploring calixarene-based clusters for efficient functional presentation of Streptococcus pneumoniae saccharides

Calixarenes are promising scaffolds for an efficient clustered exposition of multiple saccharide antigenic units. Herein we report the synthesis and biological evaluation of a calix[6]arene functionalized with six copies of the trisaccharide repeating unit of Streptococcus pneumoniae (SP) serotype 19F. This system has demonstrated its ability to efficiently inhibit the binding between the native 19F capsular polysaccharide and anti-19F antibodies, despite a low number of exposed saccharide antigens, well mimicking the epitope presentations in the polysaccharide. The calix[6]arene mobile scaffold has been selected for functionalization with SP 19F repeating unit after a preliminary screening of four model glycocalixarenes, functionalized with N-acetyl mannosamine, and differing in the valency and/or conformational properties. This work is a step forward towards the development of new fully synthetic calixarenes comprising small carbohydrate antigens as potential carbohydrate-based vaccine scaffolds

Glyco-gold nanoparticles : synthesis and applications

Glyco-gold nanoparticles combine in a single entity the peculiar properties of gold nanoparticles with the biological activity of carbohydrates. The result is an exciting nanosystem, able to mimic the natural multivalent presentation of saccharide moieties and to exploit the peculiar optical properties of the metallic core. In this review, we present recent advances on glyco-gold nanoparticle applications in different biological fields, highlighting the key parameters which inspire the glyco nanoparticle design

Epidemiological and clinical characteristics and behaviours of individuals with newly diagnosed HIV infection: a multicentre study in North Italy

ntroduction. We aimed to investigate socio-demographic, clini- cal and epidemiological characteristics and behaviours of sub- jects with new HIV diagnosis. Methods. We carried out a multi-centre cross-sectional study com- prising 17 Infectious Diseases Units in the Lombardy Region, North Italy. All subjects with a first positive test for HIV infection examined in 2008-09 were interviewed using a structured questionnaire. Results. 472 patients were enrolled (mean age 39.8 years, stand- ard deviation [SD] 11.5), mostly males (78%), and born in Italy (77%). The most common routes of HIV transmission were het- erosexual intercourse (49%) and sex among men who have sex with men (MSM) (40%). Never/sometimes use of a condom with occasional partners was associated with male gender, hetero- sexual transmission route, and with > 10 sexual partners in their lifetime. 47% had previous HIV negative tests. Having had more than 2 previous HIV negative tests was associated with younger age, MSM transmission route, CD4 + lymphocyte count ? 350/?l and self-perception of risk. Discussion. This study shows that there is a large portion of the adult population, especially heterosexual men aged 45 years and over, who are at high risk of acquiring and transmitting HIV infection and undergoing the HIV diagnostic test late, due to risk behaviours combined with a low perception of being at risk. Com- pared to people infected by heterosexual contacts, MSM show a greater awareness of being at risk of infection, but this knowledge has a low impact in reducing at-risk behaviours

Molecular dynamics simulations of the Salmonella typhi Vi antigenic polysaccharide and effects of the introduction of a zwitterionic motif

A series of hexasaccharides corresponding to the Vi capsular polysaccharide, a polymer of \u3b1-(1\u21924)-galacturonic acid, and analogs containing a zwitterionic motif with various degrees of acetylation at positions 3 have been modeled. When submitted to molecular dynamics simulations in a water box, all the structures visited only two quite restricted regions of the /\u3c8 conformational space both corresponding to extended geometries without any tendency towards supercoiling. The most stable conformation showed a clockwise helix arrangement of substituents on the molecular surface whereas the opposite arrangement was observed for the other conformation. The flexibility of the system and the hydrophobic character of the molecular surface are modulated by the 3-O-acetyl groups that confer rigidity to the system. In the zwitterionic analogs, the introduction of positive charges in the place of the acetamido groups alters the hydrophobicity that can be regained by methylation of the amino groups. The needed molecular flexibility can be obtained by the complete deacetylation at positions 3

Glycan array evaluation of synthetic epitopes between the capsular polysaccharides from Streptococcus pneumoniae 19F and 19A

Vaccination represents the most effective way to prevent invasive pneumococcal diseases. The glycoconjugate vaccines licensed so far are obtained from capsular polysaccharides (CPSs) of the most virulent serotypes. Protection is largely limited to the specific vaccine serotypes, and the continuous need for broader coverage to control the outbreak of emerging serotypes is pushing the development of new vaccine candidates. Indeed, the development of efficacious vaccine formulation is complicated by the high number of bacterial serotypes with different CPSs. In this context, to simplify vaccine composition, we propose the design of new saccharide fragments containing chemical structures shared by different serotypes as cross-reactive and potentially cross-protective common antigens. In particular, we focused on Streptococcus pneumoniae (Sp) 19A and 19F. The CPS repeating units of Sp 19F and 19A are very similar and share a common structure, the disaccharide ManNAc-beta-(1 -> 4)-Glc (A-B). Herein, we describe the synthesis of a small library of compounds containing different combinations of the common 19F/19A disaccharide. The six new compounds were tested with a glycan array to evaluate their recognition by antibodies in reference group 19 antisera and factor reference antisera (reacting against 19F or 19A). The disaccharide A-B, phosphorylated at the upstream end, emerged as a hit from the glycan array screening because it is strongly recognized by the group 19 antisera and by the 19F and 19A factor antisera, with similar intensity compared with the CPSs used as controls. Our data give a strong indication that the phosphorylated disaccharide A-B can be considered a common epitope among different Sp 19 serotypes.Host-parasite interactio