Sugar-derived oxazolone pseudotetrapeptide as γ-turn inducer and anion-selective transporter.

The intramolecular cyclization of a C-3-tetrasubstituted furanoid sugar amino acid-derived linear tetrapeptide afforded an oxazolone pseudo-peptide with the formation of an oxazole ring at the C-terminus. A conformational study of the oxazolone pseudo-peptide showed intramolecular C=O···HN(II) hydrogen bonding in a seven-membered ring leading to a γ-turn conformation. This fact was supported by a solution-state NMR and molecular modeling studies. The oxazolone pseudotetrapeptide was found to be a better Cl--selective transporter for which an anion-anion antiport mechanism was established.

Acyclic αγα-Tripeptides with Fluorinated- and Nonfluorinated-Furanoid Sugar Framework: Importance of Fluoro Substituent in Reverse-Turn Induced Self-Assembly and Transmembrane Ion-Transport Activity.

Acyclic αγα-tripeptides derived from fluorinated-furanoid sugar amino acid frameworks act as reverse-turn inducers with a U-shaped conformation, whereas the corresponding nonfluorinated αγα-tripeptides show random peptide conformations. The NMR studies showed the presence of bifurcated weak intramolecular hydrogen bonding (F···HN) and N+···Fδ- charge-dipole attraction compel the amide carbonyl groups to orient antiperiplanar to the C-F bond, thus, demonstrating the role of the fluorine substituent in stabilizing the U-shaped conformation. The NOESY data indicate that the U-shaped tripeptides self-assembly formation is stabilized by the intermolecular hydrogen bonding between C═O···HN with antiparallel orientation. This fact is supported by ESI-MS data, which showed mass peaks up to the pentameric self-assembly, even in the gas phase. The morphological analysis by FE-SEM, on solid samples, showed arrangement of fibers into nanorods. The antiparallel self-assembled pore of the fluorinated tripeptides illustrates the selective ion-transport activity. The experimental findings were supported by DFT studies.

Self-Assembly of Fluorinated Sugar Amino Acid Derived α,γ-Cyclic Peptides into Transmembrane Anion Transport.

Syntheses of fluorinated sugar amino acid derived α,γ-cyclic tetra- and hexapeptides are reported. The IR, NMR, ESI-MS, CD, and molecular modeling studies of cyclic tetra- and hexapeptides showed C2 and C3 symmetric flat oval- and triangular-ring shaped ß-strand conformations, respectively, which appear to self-assemble into nanotubes. The α,γ-cyclic hexapeptide (EC50 = 2.14 µM) is found to be a more efficient ion transporter than α,γ-cyclic tetrapeptide (EC50 = 14.75 µM). The anion selectivity and recognition of α,γ-cyclic hexapeptide with NO3- ion is investigated.