α,ε-Hybrid Foldamers with 1,2,3-Triazole Rings: Order versus Disorder

Two
epimeric series of foldamers characterized by the presence
of a repeating α,ε-dipeptide unit have been prepared and
characterized by 1H NMR and ECD spectroscopies together
with X-ray diffraction. The first series contains l-Ala and d-4-carboxy-5-methyl-oxazolidin-2-one (d-Oxd). The
other series contains l-Ala and l-Oxd. The l,d series of oligomers forms ordered β-turn foldamers,
characterized by a 311 pattern. The l,l series is not ordered. Simulations show that an ordered l,l trimer lies more than 2 kcal/mol higher than the more
stable nonfolded extended conformations. Cu2+ forms complexes
with both series but is not able to order the l,l series. Analysis of the EPR spectra shows that the l,d foldamers bear two types of complexation sites that are assigned
as a nitrogen donor of the triazole ring and a carboxylate ligand.
The l-Ala-d-Oxd-Tri-CO motif may be introduced in
any peptide sequence requiring the presence of a stable β-turn
conformations, like in the study of protein–protein interactions.