title: Design, synthesis, and NMR structure of linear and cyclic oligomers containing novel furanoid sugar amino acids.
abstract: Sugar Amino Acids (SAAs) are sugar moieties containing at least one amino and one carboxyl group. The straightforward synthesis of two furanoid SAAs, 3-amino-3-deoxy-1,2-isopropylidene-alpha-D-ribofuranoic acid (f-SAA1) and 3-amino-3-deoxy-1,2-isopropylidene-alpha-D-allofuranoic acid (f-SAA2) starting from diacetone glucose, is described. These SAAs were used as structural templates aiming at new structures for peptidomimetic drug design. f-SAA1 resembles a beta-amino acid, whereas f-SAA2 is a gamma-amino acid mimetic. Thus, for the synthesis of the mixed, linear and cyclic oligomers of f-SAA1, beta-homo-glycine (beta-hGly, also called beta-alanine) was chosen as an amino acid counterpart, while for the oligomer of f-SAA2 gamma-amino butyric acid (GABA) was chosen. Fmoc-[f-SAA1-beta-hGly](3)-OH (3) and cyclo[f-SAA1-beta-hGly](3) (5) resemble linear and cyclic beta-peptides with a very different substitution pattern, compared with the beta-peptides known so far in the literature, whereas Fmoc-[f-SAA2-GABA](3)-OH (4) resembles a gamma-peptide. The linear f-SAA oligomers 3 and 4 were synthesized on the solid-phase using Fmoc strategy. 23 unambiguous interresidue NOE contacts (from a total of 76 NOE values), obtained from extensive NMR studies in C(3)CN, were used in subsequent simulated annealing and MD calculations, to elucidate the 12/10/12-helical structure of oligomer 3 in CH(3)CN. The results indicate that f-SAA1 strongly induces a secondary structure. A characteristic CD curve for the linear oligomer 3 is observed up to 75 degrees C in both CH(3)CN and CH(3)CN/H(2)O, even though 3 contains beta-hGly, which is known to destabilize helices. By contrast, 4 does not seem to form a stable conformation in solution. The cyclic SAA containing oligomer cyclo [f-SAA1-beta-hGly](3) (5) exhibits a C(3) symmetric conformation on the NMR chemical shift time scale.
mesh_terms: D000596:Amino Acids / Q000737:chemistry*; D002236:Carbohydrate Conformation; D002241:Carbohydrates / Q000737:chemistry*; D002942:Circular Dichroism; D003500:Cyclization; D005663:Furans / Q000737:chemistry*; D006860:Hydrogen Bonding; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D010456:Peptides, Cyclic / Q000737:chemistry
chemical_list: D000596:Amino Acids; D002241:Carbohydrates; D005663:Furans; D010456:Peptides, Cyclic