Solid Phase Synthesis and Secondary Structural Studies of (1→5) Amide-Linked Sialooligomers¹

Abstract

A series of dimeric through octameric (1→5) amide-linked sialooligomers were prepared using solid-phase peptide methods on Rink resin with Fmoc protecting group chemistry. The oligomers were conjugated to ε-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.

Gramicidin S Derivatives Containing cis‐ and trans‐Morpholine Amino Acids (MAAs) as Turn Mimetics

“…In case of compound 6 this is the expected outcome since we and others have designed and synthesized related turn mimetics, such as sugar amino acids (SAAs), having cis configured aminomethyl-and carboxyl groups functionalities. [23][24][25][26][27][28][29][30][31][32][33][34][35][36][37] However, in general trans isomers are considered as mimetics of extended conformations and we were thus somewhat surprised to observe that also compound 8 assumes a secondary structure strongly resembling that of GS, with all four intramolecular hydrogen bonds apparently in place. It can be assumed that the octapeptide sequence originating from GS overrules a possible intrinsic conformational preference that MAA 4 would transpose to a linear oligopeptide.…”

Synthesis of Glycidol‐ and Sugar‐Derived Bicyclic β‐ and γ/δ‐Amino Acids for Peptidomimetic Design

“…[4] Recently, γ-and δ-amino acids gathered the same interest. In particular, the folding properties of γ- [5] and δ-peptides [6] have been investigated, as they proved to generate stable secondary structures. β-Amino acids are found in many naturally occurring peptides as key components, [7] and also exhibit pharmaco-logical properties as single compounds.…”

Polyol Peptidomimetics

“…2000, 1113Ϫ1120 1116 lactone before the condensation with cysteine. -Glucurono-3,6-lactone selectively forms an acetonide [20] which was converted into the protected amino acid in either the gluco- (10) or the ido- (11) configuration. [21] The acetonide in 10 was cleaved with TFA and the condensation with -cysteine methyl ester gave the Boc-protected dipeptide 12, as described in our preliminary publication.…”

“…[9] Similar concepts are pursued with the so-called sugar-amino acids [10] and other amide-linked oligosaccharides. [11] The strategy summarised in Scheme 1 combines the rigidity of Scheme 1 tected and selectively elongated to the pseudo-tripeptide 16. The depsipeptide 17 was obtained by condensation of BocAla-OH with the polyol 2.…”