Convergent total synthesis of a tumour-associated mucin motif.

摘要: Synthetic glycoconjugates that mimic cell-surface tumour antigens (glycolipids or glycoproteins with unusual carbohydrate structural motifs) have been shown to trigger humoral responses in murine and human immune systems1,2,3. This raises the exciting possibility of inducing active immunity fully synthetic vaccines, particularly if vaccine compounds can be synthesized resemble surface environment transformed cells even more closely. Glycopeptides seem suitable for this purpose. In contrast most glycolipids thecarbohydrates themselves, glycopeptides bind major histocompatibility complex molecules, and, favourable cases, stimulate T lead expression receptors recognize part a glycopeptide high specificity4,5,6,7,8. The preparation remains, however, difficult challenge9,10,11,12: earlier synthesis methods inefficient, established cloning approaches allow engineering global glycopatterns produce only heterogeneous glycoproteins13. Here we report an efficient strategy tumour-associated mucin clustered trisaccharide glycodomains corresponding (2,6)-sialyl antigen. Our approach involves construction complete glycodomain first stage, followed by convergent coupling amino acid residues subsequent incorporation glycosyl units into peptide chain. general allows assembly molecules which selected glycoforms incorporated at any desired position resultant O-linked clusters are closest homogeneous mimics mucins present available, so promising development anticancer vaccines.