Extended Apolar β-Peptide Foldamers: The Role of Axis Chirality on β-Peptide Sheet Stability

This study is on structure and stability of sheetlike conformers of beta-peptides; never seen new foldamers are reported here for the first time. Single- and double-stranded structures are analyzed, and the seeds of large beta-layers and biocompatible nanomaterials are described here. Both the monomeric, HCO-[NH-CH2-CH2CO](n)-NH2, and dimeric forms, [HCO-(beta-Ala)(n)-NH2](2), n = 3 and 4, of oligo-beta-alanine supramolecular complexes are evaluated by using an adequate level of theory M052X/6-31G(d) for peptides of this size. Polymers composed of backbone foklamers with the central p torsion angle set to an anti orientation were all probed. Sheet structures built up of strands with carbonyl groups monotonically facing the same spatial direction, polar strands, were previously assigned and synthesized (Seebach, D. Chem. Biodiversity 2004, 1, 1111-1239). Now we are presenting a novel beta-peptide sheet structure of alternating carbonyl group orientations, called as apolar strands. These novel secondary structural elements of beta-peptides are structural analogs of beta-pleated sheets of proteins. Interestingly enough, the latter type of apolar strands are foreseen as very stable supramolecular complexes and are more firm by similar to 10 kcal.mol(-1) than the aforementioned polar strands. Furthermore, apolar strands lack the inherent twisting of beta-layers, present in polar strands resulting in the tubular shape. Once the effect of substitution of H beta 1 and/or H beta 2 atoms are revealed on foldamer stability, short peptide sequence could be designed and synthesized. These new, conformationally optimized beta-sheetlike nanostructures of increased stability with little or no twisting could be used as enzymatically resistant (Frackenpohl, J.; Arvidsson, P. I.; Schreiber, J. V.; Seebach, D. ChemBioChem 2001, 2, 445-455) biomaterials. These newly designed models systems could enlarge the arsenal of durable polyesters of similar chemical constitution (e.g., [O-CH(CH3)-CH2CO](n)(-) and -[O-CH(COOH)-CH2CO](n)(-)) already used as artificial heart valves, for example.