Search

This study is on structure and stability of sheetlike conformers of β-peptides; never seen new foldamers are reported here for the first time. Single- and double-stranded structures are analyzed, and the seeds of large β-layers and biocompatible nanomaterials are described here. Both the monomeric, HCO-[NH-CH2-CH2CO]n-NH2, and dimeric forms, [HCO-(β-Ala)n-NH2]2n= 3 and 4, of oligo-β-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 foldamers with the central μ 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. Biodiversity2004, 1, 1111−1239). Now we are presenting a novel β-peptide sheet structure of alternating carbonyl group orientations, called as apolar strands. These novel secondary structural elements of β-peptides are structural analogs of β-pleated sheets of proteins. Interestingly enough, the latter type of apolar strands are foreseen as very stable supramolecular complexes and are more firm by ∼10 kcal·mol−1than the aforementioned polar strands. Furthermore, apolar strands lack the inherent twisting of β-layers, present in polar strands resulting in the tubular shape. Once the effect of substitution of Hβ1 and/or Hβ2 atoms are revealed on foldamer stability, short peptide sequence could be designed and synthesized. These new, conformationally optimized β-sheetlike nanostructures of increased stability with little or no twisting could be used as enzymatically resistant (Frackenpohl, J., Arvidsson, P. I., Schreiber, J. V., and Seebach, D.ChemBioChem2001, 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. [ABSTRACT FROM AUTHOR]

Non-reactive, comparative (2 × 1.2 μs) molecular dynamics simulations were carried out to characterize the interactions between glutathione (GSH, host molecule) and hydroxyl radical (OH(•), guest molecule). From this analysis, two distinct steps were identified in the recognition process of hydroxyl radical by glutathione: catching and steering, based on the interactions between the host-guest molecules. Over 78% of all interactions are related to the catching mechanism via complex formation between anionic carboxyl groups and the OH radical, hence both terminal residues of GSH serve as recognition sites. The glycine residue has an additional role in the recognition of OH radical, namely the steering. The flexibility of the Gly residue enables the formation of further interactions of other parts of glutathione (e.g. thiol, α- and β-carbons) with the lone electron pair of the hydroxyl radical. Moreover, quantum chemical calculations were carried out on selected GSH/OH(•) complexes and on appropriate GSH conformers to describe the energy profile of the recognition process. The relative enthalpy and the free energy changes of the radical recognition of the strongest complexes varied from -42.4 to -27.8 kJ/mol and from -21.3 to 9.8 kJ/mol, respectively. These complexes, containing two or more intermolecular interactions, would be the starting configurations for the hydrogen atom migration to quench the hydroxyl radical via different reaction channels.