Elusive π-helical peptide foldamers spotted by chiroptical studies.

A series of oligomers containing alternate l-Ala and pGlu (pyroglutamic acid) both in the L and D form have been prepared and conformationally investigated by X-ray, NMR, UV/ECD, IR/VCD and molecular modelling. X-ray diffraction analysis was possible for the shortest oligomers LL-1 and LD-1. Molecular dynamics simulations of the oligomers demonstrated that the energy landscapes of the LL-series are broad. In contrast, the energy landscapes of the LD-series are characterized by well-defined minima corresponding to specific conformational structures. A single well-defined minimum exists in the energy landscape of the largest oligomer LD-8, corresponding to a precise conformation, characterized by i + 5 →i N-HO[double bond, length as m-dash]C hydrogen bonds, typical of a π-helix. ECD and VCD spectra were measured to identify the chiroptical profiles of the oligomers. The most striking element in the ECD spectra of the LD-series is their exceptionally strong intensity, which confirms that these polypeptides attain a high degree of helical order. VCD spectra for the LD-series are well reproduced by frequency calculations when π-helix folds are employed as input structures, suggesting that a symmetrical VCD couplet around 1720 cm-1 can be taken as the VCD signature of π-helices.

Interactions between Endohedral Metallofullerenes and Proteins: The Gd@C60-Lysozyme Model.

Endohedral metallofullerenes (EMFs) have great potential as radioisotope carriers for nuclear medicine and as contrast agents for X-ray and magnetic resonance imaging. EMFs have still important restrictions for their use due to low solubility in physiological environments, low biocompatibility, nonspecific cellular uptake, and a strong dependence of their peculiar properties on physiological parameters, such as pH and salt content. Conjugation of the EMFs with proteins can overcome many of these limitations. Here we investigated the thermodynamics of binding of a model EMF (Gd@C60) with a protein (lysozyme) that is known to act as a host for the empty fullerene. As a rule, even if the shape of an EMF is exactly the same as that of the related fullerene, the interactions with a protein are significantly different. The estimated interaction energy (ΔG binding) between Gd@C60 and lysozyme is -18.7 kcal mol-1, suggesting the possibility of using proteins as supramolecular carriers for EMFs. π-π stacking, hydrophobic interactions, surfactant-like interactions, and electrostatic interactions govern the formation of the hybrid between Gd@C60 and lysozyme. The comparison of the energy contributions to the binding between C60 or Gd@C60 and lysozyme suggests that, although shape complementarity remains the driving force of the binding, the presence of electron transfer from the gadolinium atom to the carbon cage induces a charge distribution on the fullerene cage that strongly affects its interaction with the protein.