Three-Dimensional Arrangement of Sugar Residues along a Helical Polypeptide Backbone: Synthesis of a New Type of Periodic Glycopeptide by Polymerization of a β-O-Glycosylated Tripeptide Containing α-Aminoisobutyric Acid

A new type of glycopeptide having a periodic sequence of -[L-Glu(OMe)-Ser(beta-D-GlcNAc)-Aib]- was synthesized by polymerization of a glycosylated tripeptide with diphenylphosphoryl azide (DPPA) and active ester methods using H-L-Glu(OMe)-Ser[beta-D-GlcNAc(Ac)(3)]-Aib-OH (13) and H-L-Glu(OMe)-Ser[beta-D-GlcNAc(Ac)(3)]-Aib-ONp (15, Np = p-nitrophenyl) as the monomers, respectively. Number-average molecular weights were determined by size exclusion chromatography (SEC) and matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry, those in the latter method were higher than those in the former one. CD and FT IR spectra of poly(13) and poly(15) indicated that they form right-handed helical conformations. Deacetylation of the acetylated glycopeptide was established without racemization using hydrazine/methanol. CD spectra of the deacetylated glycopeptides 16 (21 and 24 residues) in water showed negative Cotton effect at wavelength of 208 and 222 nm indicating an alpha-helical conformation, i.e., N-acetyl-D-glucosamine (GlcNAc) moieties were arranged spatially along the alpha-helical peptide keeping a specific distance and orientation in water. Addition of ethanol to aqueous solutions of the periodic glycopolymer 16 resulted in an increase in the alpha-helix content. Semiempirical molecular orbital calculation also supported the alpha-helical conformation of 16.