beta-Peptides: from structure to function.

Palladium catalysis for the intramolecular amination of alkenes is a powerful approach in heterocycle synthesis. The initial common step in this approach consists of an aminopalladation reaction. This tutorial review describes the synthesis of 2-amino alkyl–palladium compounds and renders special attention on the subsequent manipulation of the alkyl-palladium group. By carefully choosing the appropriate conditions, a wide variety of different heterocyclic structures are accessible which arise from reactions such as hydroamination, aza-Heck coupling, aminocarbonylation or oxidative processes such as aza-Wacker reaction and 1,2-difunctionalisation.

Intramolecular aminopalladation of alkenes as a key step to pyrrolidines and related heterocycles

The principal secondary structural motifs adopted by peptides assembled from beta-amino acid units are discussed: the 14-, 12-, 10-, 12/10-, and 8-helices, as well as the hairpin turn, extended structures, stacks, and sheets. Features that promote a particular folding propensity are outlined and illustrated by structures determined in solution (NMR) and in the solid-state (x-ray). The N-C(beta)-C(alpha)-CO dihedral angles from molecular dynamics simulations, which are indicative of a particular secondary structure, are presented. A brief description of a helix and a turn of gamma-peptides is also given.

Helices and other secondary structures of β‐ and γ‐peptides

How we drifted into peptide chemistry and where we have arrived at

β-Peptoids are based on N-alkylated β-aminopropionic acid residues, which have been inspired by the more intensely studied peptoids and β-peptides Here, the authors report X-ray crystal structures of oligomeric β-peptoids demonstrating secondary structures with this backbone

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Triangular prism-shaped β-peptoid helices as unique biomimetic scaffolds

To study the role of H-bonds in stabilizing β-peptidic secondary structures, we have synthesized β-oligopeptides (up to the octadecamer 12) consisting of β2- and β3-homoproline, i.e., β-peptides lacking amide protons. The enantiomer purity of the building block β2-homoproline (nipecotic acid, 4) was determined by HPLC analysis of the N-(2,4-dinitrophenyl) derivative 5 on a Chiralcel-OD column (cf. Fig. 2). The CD spectra of the all-(S)-β2- and all-(S)-β3-HPro-containing β-peptides display novel and intensive CD patterns which may be indicative of a secondary structure (cf. Fig. 3). It is noteworthy that a distinct CD pattern was observed with the β3-HPro derivatives containing as few as three residues (7a). The crystal structure of a N-deprotected β3-HPro-tripeptide 7c is presented (cf. Figs. 4 and 5), and a model for the structure of β-peptides consisting of β3-HPro is discussed (cf. Figs. 6 and 7).

Kurt Vögtli

Papers

Oligomers ofβ2- and ofβ3-Homoproline: What are the Secondary Structures ofβ-Peptides Lacking H-Bonds?