A Facile Silyl Linker Strategy for the Solid-Phase Synthesis of Protected Glycopeptide: Synthesis of an N-Terminal Fragment of IL-2 (1–10)

An N-terminal glycodecapeptide fragment of interleukin 2 (1) was synthesized by solid-phase method utilizing a new silyl linker. The O-silylated Fmoc–Thr–OAll was attached to the commercial HMP-resin and peptide chain elongation was performed by Fmoc protocol to produce a protected heptapeptide (3–10), which was cleaved from the resin by fluoridolysis and used as the amino component for further condensation on the solid support. On the other hand, 6-hydroxyl group of an Fmoc–Thr(GalNAc)–OAll derivative was silylated with the linker and attached to the resin. Deallylation, block condensation with the heptapeptide (3–10), and elongation at N-terminal with two amino acids were performed on the resin. Fluoride ion-mediated cleavage released the N- and C-protected glycopeptide from the solid support in good efficiency. Fully deprotected glycopeptide was also synthesized through on-resin deallylation and acidic cleavage of the silyl ether linkage.