Facile solid-phase synthesis of an antifreeze glycoprotein

The antifreeze glycoproteins (AFGPs) 1 are composed of a repeating tripeptide unit (Ala-Thr-Ala) in which the threonine residue is glycosylated with the disaccharide β-D-Gal-(1 → 3)-α-D-GalNAc. A new procedure for synthesizing AFGPs using Fmoc-(Ac₄-β-D-Gal-(1 → 3)-benzylidene-α-D-GalNAc)Thr-OH (10) as a building block has been developed. Total synthesis of the AFGPs (n=4, 8) in overall yields of 61% and 33%, respectively, has demonstrated the usefulness of the method. The synthetic AFGPs 1 (n=4, 8) showed a similar conformation to the native AFGPs in their circular dichroism spectra.