Studies on the interactions between glycosylated beta3-peptides and the lectin Vicia villosa by saturation transfer difference NMR spectroscopy.

Saturation transfer difference (STD) NMR spectroscopy was used to study the interaction of the lectin Vicia villosa (VVLB(4)) with alpha-D-GalNAc glycosylated beta(3)-peptides. The data were compared to those obtained with the monosaccharides D-Gal, D-GalNAc, and D-Glc as well as with those obtained with the Tn antigen alpha-glycopeptide (D-GalNAc-alpha-O-Ser/Thr), molecule naturally recognized by V. villosa.

Design and synthesis of glycosylated beta3-peptides capable of folding into the 3(14)-helical conformation in water.

Herein, we describe the synthesis of seven glycosylated beta(3)-peptides, 1-7, which were designed to adopt stable 3(14)-helical conformations in aqueous solution. Such molecules are representative for a novel class of functionalized foldamers in which a natural post-translational modification is attached to an unnatural peptidomimetic backbone. Conformational studies by CD spectroscopic measurements were performed in methanol and in water (pH 7).

Glycosylated foldamers: synthesis of carbohydrate-modified beta3hSer and incorporation into beta-peptides.

Fmoc-protected beta(3)hserine (beta(3)hSer) was prepared and O-linked to suitably protected N-acetylgalactosamine (GalNAc) and N-acetylglucosamine (GlcNAc) derivatives. Glycosylation of beta(3)hSer was made by two independent routes: either by direct glycosyl linkage to the beta(3)hSer, or linkage to natural L-Ser and then utilizing the carbohydrate moiety as a protecting group in an Arndt-Eistert homologation. Both procedures gave the novel glycosylated beta(3)-amino acids Fmoc-beta(3)hSer(alpha-D-GalNAc(Ac)(3))-OH (1a), its beta-anomer (1b), and Fmoc-beta(3)hSer(beta-D-GlcNAc(Ac)(3))-OH (2), which were utilized in the solid-phase peptide synthesis of four glycosylated dipeptides (3a-d) and two heptapeptides (4a-b).

Biomolecular recognition of glycosylated beta(3)-peptides by GalNAc specific lectins.

The molecular recognition of a novel kind of hybrid conjugates, composed of artificial biomimetic beta-peptide oligomers with an O-linked natural N-acetyl-galactosamine (the Tn-antigen) residue, by four different GalNAc specific lectins was investigated using surface plasmon biosensor technology. The influence of the peptide and the glycosyl moiety on the recognition was studied using two glycosylated beta(3)-heptapeptides, a glycosylated alpha-heptapeptide, two beta-amino acid containing dipeptides, and monomeric alphaGalNAc-O-Thr. Although all four lectins displayed a decreased affinity for the carbohydrate residue when attached to a peptide, as compared to the monomeric Tn-antigen, the peptide part was found to have distinct effects on the binding kinetics-indicating that varying degrees of protein-peptide interactions occurred in the recognition process.

Synthesis and circular dichroism spectroscopic investigations of oligomeric beta-peptoids with alpha-chiral side chains.

Biomimetic oligomers are of large interest both as targets for combinatorial and parallel synthetic efforts and as foldamers. For example, shorter peptoid derivatives of beta-peptides, i.e.

Beta2-amino acids in the design of conformationally homogeneous cyclo-peptide scaffolds.

Herein, we report studies on the influence of chiral beta(2)-amino acids in the design of conformationally homogeneous cyclic tetrapeptide scaffolds. The cyclic alpha-tetrapeptide cyclo(-Phe-D-Pro-Lys-Phe-) (1) and its four mixed analogues, having one of the alpha-Phe replaced by either an (S)- or an (R)-beta(2)hPhe residue (i.e.

Cyclic beta-tetra- and pentapeptides: synthesis through on-resin cyclization and conformational studies by X-ray, NMR and CD spectroscopy and theoretical calculations.

The solution-phase synthesis of the simplest cyclic beta-tetrapeptide, cyclo(beta-Ala)4 (4), as well as the solid-phase syntheses through side chain anchoring and on-resin cyclization of the cyclic beta3-tetrapeptide cyclo(-beta3hPhe-beta3hLeu-beta3hLys-beta3hGln-) (14) and the first cyclic beta3-pentapeptide cyclo(-beta3hVal-beta3hPhe-beta3hLeu-beta3hLys-beta3hLys-) (19) are reported. Extensive computational as well as spectroscopic studies, including X-ray and NMR spectroscopy, were undertaken to determine the preferred conformations of these unnatural oligomers in solution and in the solid state. cyclo(beta-Ala)4 (4) with no chiral side chains is shown to exist as a mixture of rapidly interchanging conformers in solution, whereas inclusion of chiral side chains in the cyclo-beta3-tetrapeptide causes stabilization of one dominating conformer.

Functionalized foldamers: synthesis and characterization of a glycosylated beta-peptide 314-helix conveying the TN-antigen.

Herein we describe the design, synthesis, and solution structure of a novel type of conjugate composed of a naturally occurring bio-active ligand bound to an artificial peptidomimetic backbone; in this first report on such functionalized foldamers we utilized a beta-peptide as backbone and a GalNAc carbohydrate residue as ligand.