<p>The removal of the glycosidic phosphate from the reducing end of the derived LPS molecule creates an aldehydo functionality which causes the formation of an immunologically dominant neo-epitope. Conjugation to the reducing end of a carbohydrate molecule following removal of the glycosidic phosphate traps the reducing glucosamine residue in an open-chain form which surprisingly was found to dominate the immune response. We therefore modified our conjugation strategy to avoid this open-chain form, by utilising the amino functionality created by the isolated amidase activity from Dictyostelium discoideum, concomitant with a unique blocking and un-blocking strategy to protect the immunologically important phosphoethanolamine inner core residue. These antigenic structures are useful in producing vaccines and compounds helpful in combating Gram-negative bacteria. Also described are specific structures of the carbohydrate molecules derived from a variety of Gram-negative bacteria, which when presented appropriately as a glycoconjugate will facilitate a functional immune response to the target core oligosaccharide region.</p>
申请公布号
WO2010025542(A1)
申请公布日期
2010.03.11
申请号
WO2009CA01201
申请日期
2009.09.08
申请人
NATIONAL RESEARCH COUNCIL OF CANADA;COX, ANDREW, D.;ST. MICHAEL, FRANK;RICHARDS, JAMES, C.;MOXON, E. RICHARD
发明人
COX, ANDREW, D.;ST. MICHAEL, FRANK;RICHARDS, JAMES, C.;MOXON, E. RICHARD