Synthesis and Immunochemical characterization of S‐linked Glycoconjugate Vaccines against Candida albicans

Abstract

Replacement of the glycosidic oxygen atom by a sulphur atom is a promising technique for creating glycoconjugates with increased resistance to hydrolysis by endogenous glycosidases. The synthesis and antigenic properties of two distinct (1-->2)-beta-mannan trisaccharides with inter residue-S-linked mannopyranose residues are described. Syntheses were based on an oxidation-reduction strategy to construct the O-linked beta-mannopyranoside bonds and a SN2 inversion to provide 1-thio-beta-mannopyranoside residues. Subsequently the allyl trisaccharide glycosides were subjected to photo addition with cysteine amine and coupled to tetanus toxoid and bovine serum albumin with good efficiency via an adipic acid tether. Rabbit immunization studies revealed that the antibodies elicited by the two glycoconjugates were able to recognize the corresponding O-linked trisaccharide epitope conjugated to BSA and the native cell wall antigen of Candida albicans.

Mucin architecture behind the immune response: design, evaluation and conformational analysis of an antitumor vaccine derived from an unnatural MUC1 fragment

“… 12 One way to overcome this issue is through the use of chemical modifications of the antigens to generate non-natural determinants. 13 A number of TACA mimics, comprising C-glycosides 14 – 16 and S-glycosides, 17 – 19 have been incorporated into carbohydrate-based vaccines. Additionally, the use of homoserine and β 3 -homothreonine conjugates 20 , 21 to construct mucin-like glycopeptides and derivatives that incorporate fluorine atoms 22 , 23 have been proposed.…”

Synthesis of a-O- and a-S-Glycosphingolipids Related to Sphingomonous cell Wall Antigens Using Anomerisation

“…S-Glycosides are apparently more stable in vivo than native O-glycosides and also there is the possibility that they are more immunogenic, which is relevant to vaccine development [28]. Kinetic studies on the anomerisation of S-butyl and O-butyl glycosides, as well as the formation of 23a and 23b, indicated that anomerisation of S-glycolipids would be feasible [14].…”

“…After the addition was completed, the reaction mixture was then centrifuged at 15000 rpm for 15 min, the supernatant was removed and the precipitate washed twice with water. The precipitate was then lyophilised to give 5 (1.2 mg, 22%) as a white solid; (28). Nonadec-1-ene 27 (1.96 g, 7.37 mmol) was dissolved in CHCl 3 (15 mL) and bromine (1.44 g, 9.00 mmol) was added, and the reaction mixture was then stirred for 30 min at room temp.…”

Carbohydrates and Immunology: Synthetic Oligosaccharide Antigens for Vaccine Formulation

“…Further studies by Bundle and co‐workers focused on the antigenic properties of thio analogues of β‐Man oligosaccharides 209b,215. In particular, the thio‐trisaccharides 195 and 198 (Scheme ) were prepared by a synthetic route that alternatively exploited the already applied C‐2 oxidation/reduction sequence to achieve the β‐manno configuration after glycosylation of glucose donors and a S N 2 reaction with thioacetate to introduce the sulfur atom at the C‐2 position in the manno configuration 216. ELISA testing of compounds 195 and 198 revealed a higher immunogenic activity for the trisaccharide 198 while also confirming the close conformational similarity of the sulfur‐containing oligosaccharides to native O ‐linked oligosaccharides.…”