Solid phase synthesis and secondary structural studies of (1→5) amide-linked sialooligomers

A series of dimeric through octameric (1-->5) amid-linked sialooligomers were prepared using solid-phase peptide methods on Rink resin with Fmoc protecting group chemistry. The oligomers were conjugated to epsilon-amino caproic acid in order to model membrane-bound conformations. The secondary structure of the oliogomers was probed with NH/ND exchange rates determined by NMR, and with circular dichroism. The combined structural studies show that a tetramer is required for ordered secondary structure, and that secondary structure is stabilized upon elongation to pentameric and hexameric species. Interestingly, the heptamer shows rapid NH/ND exchange rates; however, ordered secondary structure is restored in the octamer. These studies provide the first evidence that oligomers composed of constrained carbohydrate-derived amino acids form stable secondary structures in water.