Peptide ligations accelerated by N-terminal aspartate and glutamate residues.

A novel application of intramolecular base catalysis confers enhanced reaction rates for aminolysis ligations between peptide thioesters and peptides bearing N-terminal aspartate or glutamate residues. The broad scope of this process and its application in the total synthesis of the diabetes drug exenatide is demonstrated.

Synthesis of MUC1-lipopeptide chimeras.

An efficient method for the convergent assembly of MUC1-lipopeptide vaccine candidates is described. Chimeras consisting of MUC1 glycopeptides (bearing multiple copies of the T(N) and T tumour-associated carbohydrate antigens) tethered to the lipopeptide immunoadjuvant Pam(3)CysSer were synthesised in high yields using a fragment-based condensation strategy.

Synthesis of MUC1 glycopeptide thioesters and ligation via direct aminolysis.

MUC1 is a cell-surface, epithelial glycoprotein that forms an essential protective barrier of cells and serves to modulate intercellular communication. During cancer progression, the dysregulation of glycosyltransferases, which serve to elongate cell-surface glycans, leads to aberrant gIycosylation patterns on this glycoprotein. This results in the presentation of well-characterized, tumor-associated carbohydrate antigens (TACAs) which represent important biomarkers for a range of epithelial cancers.

Polymer-peptide chimeras for the multivalent display of immunogenic peptides.

Chimeras of poly(n-isopropyl acrylamide) and immunogenic peptides from the cancer-associated glycoprotein MUC1 were synthesised using a combination of solid-phase peptide synthesis, RAFT polymerisation and copper-catalysed alkyne-azide cycloaddition reactions.