ABSTRACT
In this paper we present the synthesis of glyco-phosphoramidate conjugates as easily accessible analogs of glyco-phosphorous esters via the Staudinger-phosphite reaction. This protocol takes advantage of synthetically accessible symmetrical carbohydrate phosphites in good overall yields, in which ethylene or propylene linkers can be introduced between phosphorous and galactose or lactose moieties. The phosphites were finally applied for the chemoselective reaction with azido-peptides and polyazido(poly)glycerols.
Subject(s)
Azides/chemistry , Glycerol/chemistry , Glycopeptides/chemistry , Phosphites/chemistry , Dendrites/chemistry , Glycopeptides/chemical synthesis , Stereoisomerism , Substrate SpecificityABSTRACT
The covalent fusion of immunostimulatory adjuvants to immunogenic antigens is a promising strategy for the development of effective synthetic vaccines for infectious diseases. Herein, we describe the conjugation of a mycobacterial peptide antigen from the 6 kDa early secretory antigenic target (ESAT6) to a suitably functionalised trehalose dibehenate (TDB), a potent glycolipid adjuvant targeting macrophage inducible C-type lectin (Mincle).
Subject(s)
Lectins, C-Type , Trehalose , Adjuvants, Immunologic/pharmacology , Antigens , Glycolipids/pharmacology , Trehalose/pharmacology , Vaccines, SyntheticABSTRACT
A combination of classical site-directed mutagenesis, genetic code engineering and bioorthogonal reactions delivered a chemically modified barstar protein with one or four carbohydrates installed at specific residues. These protein conjugates were employed in multivalent binding studies, which support the use of proteins as structurally defined scaffolds for the presentation of multivalent ligands.