Synthesis of major histocompatibility complex class I binding glycopeptides

Four Major Histocompatibility Complex (MHC) Class I binding glycopeptides and two peptide analogues, from a cytotoxic T-lymphocyte (CTL) epitope of Sendai Virus Nucleoprotein, have been prepared using solid-phase peptide synthesis employing the following glycosyl amino acid building blocks: FmocSer(Ac 3-β-D-GlcNAc)OH 1, FmocSer(Ac3-α-D-GalN 3)OPfP 2, FmocAsn(Ac3-β-D-GlcNAc)OH 3 and FmocAsn(Ac3-β-D-GalNAc)OH 4. Previously, we examined the influence of glycosylation on peptide binding to the MHC Class I molecule and CTL recognition of these peptides. The synthesis and characterization of compounds 1-4 as well as the resulting glycopeptides is described. In addition, results of NMR investigations demonstrating that peptide K3, and glycopeptides K3-O-GlcNAc and K3-O-GalNAc, show two distinct conformations in solution as a result of cis-trans isomerization about a Tyr-Pro amide bond are reported.