Synthesis of the Highly Glycosylated Hydrophilic Motif of Extensins

Extensin, the structural motif of plant extracellular matrix proteins, possesses a unique highly glycosylated, hydrophilic, and repeating Ser(1)Hyp(4) pentapeptide unit, and has been proposed to include post-translational hydroxylation at proline residue and subsequent oligo-L-arabinosylations at all of the resultant hydroxyprolines as well as galactosylation at serine residue. Reported herein is the stereoselective synthesis of one of the highly glycosylated motifs, Ser(Galp(1))-Hyp(Araf(4))-Hyp(Araf(4))-Hyp(Araf(3))-Hyp(Araf(1)). The synthesis has been completed by the application of 2-(naphthyl)methylether-mediated intramolecular aglycon delivery to the stereoselective construction of the Ser(Galp(1)) and Hyp(Araf(n)) fragments as the key step, as well as Fmoc solid-phase peptide synthesis for the backbone pentapeptide.