Microwave-assisted solid-phase synthesis of antifreeze glycopeptides

Abstract

Microwave-assisted solid-phase synthesis allows for the rapid and large-scale preparation and structure-activity characterization of tandem repeating glycopeptides, namely monodispersed synthetic antifreeze glycopeptides (syAFGPs, H-[Ala-Thr(Galβ1,3GalNAcα1→)-Ala]n -OH, n=2-6). By employing novel AFGP analogues, we have demonstrated that of the monodispersed syAFGPn (n=2-6, degree of polymerization, DP=2-6, Mw =1257-3690 Da), syAFGP5 (DP=5, Mw =3082 Da) and syAFGP6 (DP=6, Mw =3690 Da) exhibit the ability to form typical hexagonal bipyramidal ice crystals and satisfactory thermal hysteresis activity. Structural characterization by NMR and CD spectroscopy revealed that syAFGP6 forms a typical poly-L-proline type II helix-like structure in aqueous solution whereas enzymatic modification by sialic acid of the residues at the C-3 positions of the nonreducing Gal residues disturbs this conformation and eliminates the antifreeze activity.