Investigation of acyl transfer auxiliary-assisted glycoconjugation for glycoprotein semi-synthesis.

Homogeneous glycoprotein syntheses have become possible in the last decade due to advances in chemical ligation strategies, particularly Native Chemical Ligation (NCL). For native glycoproteins this still requires laborious and technically challenging syntheses of glycopeptide components, combined with multi-segment ligation reactions. Here we explore new reactions between sugar-linked acyl transfer auxiliaries and peptide thioesters. We show that native glycoproteins are difficult to produce using this approach but various related analogues are accessible. The results show that site-specific neoglycoconjugation is a viable route to simply glycosylated proteins, which may be extended using well-documented enzymatic processes.

Novel electrochemically-mediated peptide dethiylation in processes relevant to native chemical ligation.

Here we explore electrochemical dethiylation in processes relevant to Native Chemical Ligation (NCL). NCL's reliance on the redox active amino acid cysteine and ß-mercaptamine derivatives suggests a potential role for electrochemistry. We show that the application of a 1 V potential to platinum electrodes in 0.15 M TCEP solution is sufficient to convert Cys to Ala in cyclic peptides, and to cleave the 2-mercapto-2-phenethyl class of acyl transfer auxiliary.