alpha,epsilon-Hybrid Foldamers with 1,2,3-Triazole Rings: Order versus Disorder

作者：Milli Lorenzo; Larocca Michele; Tedesco Mattia; Castellucci Nicola; Ghibaudi Elena; Cornia Andrea; Calvaresi Matteo; Zerbetto Francesco; Tomasini Claudia^*

来源：Journal of Organic Chemistry, 2014, 79(13): 5958-5969.

DOI：10.1021/jo500963n

Two epimeric series of foldamers characterized by the presence of a repeating alpha,epsilon-dipeptide unit have been prepared and characterized by H-1 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,121 series of oligomers forms ordered beta-turn foldamers, characterized by a 3(11) 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 beta-turn conformations, like in the study of protein-protein interactions.

• 出版日期2014-7-4