The principal investigator states that the importance of the project stems from the fact that of the three major families of biopolymers, proteins, oligonucleotides and oligosaccharides, the last is the least well understood because their isolation, structure-proof, and (above all) their laboratory syntheses have been far more difficult and demanding than in the case of the other two. He notes that however, great strides have been made in the techniques of isolation and structure-proof which has made many of these oligosaccharides available intact, and it is now clear that their structures are usually of daunting complexity. He further indicates that with the other two biopolymers, proteins and oligonucleotides, clarification of their biological regulatory roles accelerated markedly with the advent of synthetic methods that made them and/or their analogs, readily available for structure activity correlations. It is noted that oligosaccharides usually being the primary recognition agents on cell surfaces is now widely appreciated, this step being a prelude to subsequent critical events such as enzymolysis, cell penetration, etc and that thus bacteria, viruses, (many) hormones, other cells, etc. must engage in this first step, and hence undesirable events (such as bacterial infection) can conceivably be prevented by the use of mimics to negate the recognition step. It is further noted that on the other hand, beneficial interactions, as in the case of hormones, can be facilitated so as to enhance recognition. The principal investigator states that these visionary health-related benefits rely ultimately on ready access to synthetic oligosaccharides, or fragments and modifications thereof for biochemical evaluation and structure-activity investigations. He notes that since their discovery in his laboratory six years ago, n-pentenyl glycosides have proved to be versatile synthetic precursors for several oligosaccharides and glycoproteins and that with their credibility thereby established, he envisages greatly extending their synthetic potential to address problems associated with major health hazards. It is stated that examples of these include the lipopolysaccharides associated with Leishmaniasis and the endotoxin from lipid A and that exploratory studies aimed at developing methodology for these targets is an important segment of the proposal.
| Schofield, L; McConville, M J; Hansen, D et al. (1999) CD1d-restricted immunoglobulin G formation to GPI-anchored antigens mediated by NKT cells. Science 283:225-9 |
| Debenham, J S; Debenham, S D; Fraser-Reid, B (1996) N-Tetrachlorophthaloyl (TCP) for ready protection/deprotection of amino sugar glycosides. Bioorg Med Chem 4:1909-18 |
