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

Abstract

Two epimeric series of foldamers characterized by the presence of a repeating α,ε-dipeptide unit have been prepared and characterized by (1)H 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. Cu(2+) 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.

Pseudopeptide‐Based Hydrogels Trapping Methylene Blue and Eosin Y

“…This molecule belongs to ag roup of foldamers containing the 4-car-boxy-5-methyl-oxazolidin-2-one unit (Oxd) [18] or the p-glutamic acid unit (pGlu). [19] These molecules cause al ocal constraint in the pseudopeptide chain that favours the formationo fs econdary structures, [20][21][22] fibers [23][24][25] and gels. [26][27][28] Thus we prepared hydrogels based on Fmoc-l-Phe-d-pGlu-OH to test them for the adsorptiono fM ethylene Blue (MB), ac ationic dye, and Eosin Y( EY), an anionic dye, as these molecules may be used as model pollutants.…”

Chiral Gold Nanoparticles Decorated with Pseudopeptides

“…Unfortunately we were not able to grow crystals of oligomers 1, 3, or 4. As found in related foldamers, [16] the l-Ala1 α-carbon atom C22 has a H-contact with the endocyclic C=O of the neighboring d-Oxd1 residue [d(H22···O8) = 2.300(13) Å]. The crystals are monoclinic, space group P2 1 , and the unit cell comprises two molecules related by the twofold screw axis (Figure 3).…”

“…The molecule exhibits a turnlike structure. [16] However, the l-Ala2 residue has quite different conformational parameters that fall in the right-handed αhelix region of the Ramachandran plot. However, no significant H-bonding interaction is established between the carbonyl oxygen O10 and the amide group N2-HN2 of l-Ala2 [d(HN2···O10) = 2.808(16) Å], so that a ten-membered hydrogen-bonded turn (3 10 -helical structure) is not formed.…”

“…Instead, the strongest intramolecular H-bonding interaction involves amide nitrogen N2 and the d-Oxd2 carbonyl oxygen O4 [d(HN2···O4) = 2.141(18) Å]. [16] The ECD spectra of compounds 1-4 were not recorded because the spectral features related to the secondary structure are obscured around 200 nm by the very strong B transitions of trityl groups, that are removed upon formation of the AuNPs. Molecules related by the 2 1 axis are hydrogen bonded into chains through amide group N4-HN4 and carbonyl oxygen O4 [d(HN4···O4 i ) = 2.103(11) Å], but crystal packing also relies on a number of other short C-H···O contacts (Table S3).…”

Straightforward strategy to substitute amide bonds by 1,2,3‐triazoles in peptaibols analogs using Aibψ[Tz]‐Xaa dipeptides

“…Nevertheless, considering that the distance between the side chains of two consecutive residues are increased when the amide bond is replaced by a triazole moiety, such a modification should have an impact on the biological and conformational properties of the peptides (Figure ). In addition, the modification of peptide backbones by insertion of the triazole moiety as a peptide bond mimic is poorly understood and its influence on the folding behavior of peptide was scarcely explored . In this context, we propose to study the ability of 1,4‐disubstituted‐1,2,3‐triazole to mimic the trans‐amide bond monitoring its impact on the conformation and the biological activity of peptaibols.…”