Geometrically Precise Building Blocks: the Self-Assembly of ß-Peptides.

Peptides comprised entirely of ß-amino acids, or ß-peptides, have attracted substantial interest over the past 25 years due to their unique structural and chemical characteristics. ß-Peptides form well-defined secondary structures that exhibit different geometries compared with their α-peptide counterparts, giving rise to their foldamer classification. ß-Peptide foldamers can be functionalized easily and are metabolically stable and, together with the predictable side-chain topography, have led to the design of a growing number of bioactive ß-peptides with a range of biological targets. The strategic engineering of chemical and topographic properties has also led to the design of ß-peptide mimics of higher-order oligomers. More recently, the ability of these peptides to self-assemble into complex structures of controlled geometries has been exploited in materials applications. The focus of this mini-review is on how the unique structural features of ß-peptide assemblies have been exploited in the design of self-assembled proteomimetic bundles and nanomaterials.

Conformational stability studies of a stapled hexa-ß3-peptide library.

A library of 14-helical hexa ß(3)-peptides was synthesized in order to determine the influence of sequence variation as well as staple size and location on conformational stability. From this study we show that appropriately stapled hexa-ß(3)-peptides can allow for a number of variations without significant perturbation of the 14-helix.

Synthesis of stapled beta3-peptides through ring-closing metathesis.

The first synthesis of carbon-stapled beta(3)-peptides is reported. The precursor beta(3)-peptides, with O-allyl beta-serines located in an i/i+3 relationship, were prepared on solid phase. We show that efficient ring-closing metathesis (RCM) of these new beta(3)-peptides proceeds smoothly either in solution or on an appropriate solid support. All products were generated with high selectivity for the E-isomer.