Blood group antigens: synthesis of TN glycopeptide related to human glycophorin AM

Abstract

Three 2‐acetamido‐2‐deoxy‐α‐d‐galactopyranose residues attached to Ser2, Thr3 Thr4 of the amino‐terminal portion of glycophorin AM are responsible for the so‐called TN blood group specificity. In a continuation of earlier work, this report describes the first chemical synthesis of the triglycosylated pentapeptide H2N‐Ser1‐Se*r2‐Th*r3‐Th*r4‐Gly5‐OH, in which (*) represents the 2‐acetamido‐2‐deoxy‐α‐d‐galactopyranosyl residue. This compound constitutes the G1‐G5 sequence of the amino‐terminal portion of human glycophorin AM, the main erythrocyte membrane glycoprotein. The above compound was obtained by a stepwise peptide coupling strategy alternatively using aminoacids and adequately protected and/or activated O ‐glycosyl‐aminoacids. Since the desired sequence possesses both unglycosylated and glycosylated serine this route was preferred to that in which the glycosylation is carried out on the preformed pentapeptide H2N‐Ser‐Ser‐Thr‐Thr‐Gly‐OH. Carbohydrate residues were introduced into the sequence as 2‐azido‐2‐deoxy‐α‐d‐galactopyranosyl‐l‐serine and l‐threonine derivatives. The azido functions were further converted into the corresponding acetamido groups by treatment of the final triglyco‐pentapeptide with sodium borohydride in the presence of nickel chloride followed by acetylation.