Generation of glucosylated -1-glycerolphosphate teichoic acids: glycerol stereochemistry affects synthesis and antibody interaction.
Francesca Berni, Liming Wang, Ermioni Kalfopoulou, D Linh Nguyen, Daan van der Es, Johannes Huebner, Herman S Overkleeft, Cornelis H Hokke, Gijsbert A van der Marel, Angela van Diepen, Jeroen D C Codée
Author Information
Francesca Berni: Leiden Institute of Chemistry, Leiden University Einsteinweg 55 2333 CC Leiden The Netherlands jcodee@chem.leidenuniv.nl.
Liming Wang: Leiden Institute of Chemistry, Leiden University Einsteinweg 55 2333 CC Leiden The Netherlands jcodee@chem.leidenuniv.nl.
Ermioni Kalfopoulou: Division of Pediatric Infectious Diseases, Dr von Hauner Children's Hospital, Ludwig-Maximilians-University Munich Germany.
D Linh Nguyen: Department of Parasitology, Leiden University Medical Center Albinusdreef 2 2333 ZA Leiden The Netherlands.
Daan van der Es: Leiden Institute of Chemistry, Leiden University Einsteinweg 55 2333 CC Leiden The Netherlands jcodee@chem.leidenuniv.nl.
Johannes Huebner: Division of Pediatric Infectious Diseases, Dr von Hauner Children's Hospital, Ludwig-Maximilians-University Munich Germany.
Herman S Overkleeft: Leiden Institute of Chemistry, Leiden University Einsteinweg 55 2333 CC Leiden The Netherlands jcodee@chem.leidenuniv.nl.
Cornelis H Hokke: Department of Parasitology, Leiden University Medical Center Albinusdreef 2 2333 ZA Leiden The Netherlands. ORCID
Gijsbert A van der Marel: Leiden Institute of Chemistry, Leiden University Einsteinweg 55 2333 CC Leiden The Netherlands jcodee@chem.leidenuniv.nl. ORCID
Angela van Diepen: Department of Parasitology, Leiden University Medical Center Albinusdreef 2 2333 ZA Leiden The Netherlands.
Jeroen D C Codée: Leiden Institute of Chemistry, Leiden University Einsteinweg 55 2333 CC Leiden The Netherlands jcodee@chem.leidenuniv.nl. ORCID
Lipoteichoic acids (LTAs) have been addressed as possible antigen candidates for vaccine development against several opportunistic Gram-positive pathogens. The study of structure-immunogenicity relationship represents a challenge due to the heterogenicity of LTA extracted from native sources. LTAs are built up from glycerol phosphate (GroP) repeating units and they can be substituted at the C-2-OH with carbohydrate appendages or d-alanine residues. The substitution pattern, but also the absolute chirality of the GroP residues can impact the interaction with chiral biomolecules including antibodies and biosynthesis enzymes. We have generated a set of diastereomeric GroP hexamers bearing a glucosyl modification at one of the residues. The chirality of the glycerol building block had an important impact on the stereoselectivity of the glycosylation reaction between the glycosyl donor and the glycerol C-2-OH acceptor. The GroP C-2-chirality also played an important role in the interaction with TA recognizing antibodies. These findings have important implications for the design and synthesis of synthetic TA fragments for diagnostic and therapeutic applications.
