Basic conformers in β‐peptides

Abstract

The conformation of oligomers of beta-amino acids of the general type Ac-[beta-Xaa]n-NHMe (beta-Xaa = beta-Ala, beta-Aib, and beta-Abu; n = 1-4) was systematically examined at different levels of ab initio molecular orbital theory (HF/6-31G*, HF/3-21G). The solvent influence was considered employing two quantum-mechanical self-consistent reaction field models. The results show a wide variety of possibilities for the formation of characteristic elements of secondary structure in beta-peptides. Most of them can be derived from the monomer units of blocked beta-peptides with n = 1. The stability and geometries of the beta-peptide structures are considerably influenced by the side-chain positions, by the configurations at the C alpha- and C beta-atoms of the beta-amino acid constituents, and especially by environmental effects. Structure peculiarities of beta-peptides, in particular those of various helix alternatives, are discussed in relation to typical elements of secondary structure in alpha-peptides.

Conformational preferences in the β-peptide oligomers of cis-2-amino-1-fluorocyclobutane-1-carboxylic acid

“…Further NMR studies were conducted on tetrapeptide 12 as a 15 mM solution in pyridine-d 5 . This solvent allowed the best separation of 1 H signals, and standard 1D and 2D NMR experiments were used to unambiguously assign all proton, carbon and fluorine signals.…”

“…Since the first examples of folded b-peptides reported by Gellman 2 and Seebach, 3 advances have been made in the control of the secondary structure whereby b-peptides can now be conceived to fold into helices, sheet-forming strands, or turn-like features. 4 Theoretical analyses of b-peptides suggest that a number of periodic structures may be available, 5 and while a number of the predicted helical folding patterns have been demonstrated experimentally, more extended regular structures are less well studied.…”

“…1): cis-2-aminocyclopentane-1-carboxylic acid (cis-ACPC), 7 exo-3-aminobicyclo[2.2.1]hept-5-ene-2-carboxylic acid (exo-ABHEC), 8 and cis-2-aminocyclobutane-1-carboxylic acid (cis-ACBC). 9 It was proposed that these structures might be stabilised by a series of intra-residue 6-membered ring hydrogen bonds, even though the strength of such interactions is predicted to be low, 5 which suggests that their existence is not a prerequisite to the adoption of such a conformer. 10 To further explore the propensity of oligomers of b-amino acids to adopt strand-like or related conformations, we decided to examine cis-2-amino-1-fluorocyclobutane-1-carboxylic acid (cis-FACBC) 11 (Fig.…”

β-Peptide foldamer helices with tailored diameters

“…The HF/3-21G//B3LYP/6-311G** levels of theory in vacuo were utilized, as these have been reported to provide a good approximation for the β-peptides. 200,201 The structures converged to the corresponding local minimum of the potential energy surface, except for the H10 helices, which finally converged to H14. The modelling indicated that H12 or H16 is the most likely secondary structure for the longer oligomers.…”

“…The HF/3-21 basis set in a vacuum was first utilized, as this has been reported to provide a good approximation to the geometry of β-peptides. 200,201 The structures converged to the corresponding local minimum of the potential energy surface. To take into account the effects of more diffuse basis sets and the electron correlation, the optimizations were performed at the B3/LYP/6-311G** level.…”