The first total synthesis of a glycolipid from S. pneumoniae and the biological re-evaluation of their immunological activity
Standing
Undergraduate
Type of Proposal
Oral Presentation
Faculty
Faculty of Science
Proposal
Invariant natural killer T cells (iNKT), a subclass of white blood cells, are responsible for the production of non-specific cytokines which induce a systemic uncontrolled immune response. They are distinctive in having a monospecific T-cell receptor that recognizes glycolipid antigens. The natural antigen was not identified until quite recently, when putative targets were isolated from S. pneumoniae. A bioactive fraction was identified from the extract: a disaccharide moiety attached to diacylglycerol (DAG). The glycolipid antigen reportedly activated iNKT cells. However, these tests were carried out using very small amounts of isolated glycolipids, as a result it is impossible to ascertain whether the activity was due to this compound or to some minor impurity. There was also insufficient evidence to conclusively confirm the proposed structure. Consequently, we recently synthesized the glycolipid to both confirm the structural assignment and to provide a useful chemical probe for immunologists. This presentation will discuss this S. pneumoniae glycolipid, its total synthesis, and our surprising re-evaluation of their immunological activity.
Grand Challenges
Viable, Healthy and Safe Communities
The first total synthesis of a glycolipid from S. pneumoniae and the biological re-evaluation of their immunological activity
Invariant natural killer T cells (iNKT), a subclass of white blood cells, are responsible for the production of non-specific cytokines which induce a systemic uncontrolled immune response. They are distinctive in having a monospecific T-cell receptor that recognizes glycolipid antigens. The natural antigen was not identified until quite recently, when putative targets were isolated from S. pneumoniae. A bioactive fraction was identified from the extract: a disaccharide moiety attached to diacylglycerol (DAG). The glycolipid antigen reportedly activated iNKT cells. However, these tests were carried out using very small amounts of isolated glycolipids, as a result it is impossible to ascertain whether the activity was due to this compound or to some minor impurity. There was also insufficient evidence to conclusively confirm the proposed structure. Consequently, we recently synthesized the glycolipid to both confirm the structural assignment and to provide a useful chemical probe for immunologists. This presentation will discuss this S. pneumoniae glycolipid, its total synthesis, and our surprising re-evaluation of their immunological activity.