Helical aromatic amides

The investigations of thermotropic PLCs commenced almost two decades after studies of mesophases employing rodlike polymers(21) and virus particles(22) in solution were initiated. Like their MLC analogues (aqueous solutions of amphiphilic molecules) the polymeric lyotropic liquid crystals which form in solutions of rigid, rodlike polymers (helical biopolymers, and more recently, semiflexible aromatic amides) constitute a distinct class of liquid crystals. Unlike the MLC analogues, however, the lyotropic PLCs are not necessarily stabilized by specific interactions between the polymer chain... 

A peptoid pentamer of five poro-substituted (S)-N-(l-phenylethyl)glycine monomers, which exhibits the characteristic a-helix-like CD spectrum described above, was further analyzed by 2D-NMR [42]. Although this pentamer has a dynamic structure and adopts a family of conformations in methanol solution, 50-60% of the population exists as a right-handed helical conformer, containing all cis-amide bonds (in agreement with modeling studies [3]), with about three residues per turn and a pitch of 6 A. Minor families of conformational isomers arise from cis/trans-amide bond isomerization. Since many peptoid sequences with chiral aromatic side chains share similar CD characteristics with this helical pentamer, the type of CD spectrum described above can be considered to be indicative of the formation of this class of peptoid helix in general. 

As such, the magainins provide a useful initial target for peptoid-based peptido-mimetic efforts. Since the helical structure and sequence patterning of these peptides seem primarily responsible for their antibacterial activity and specificity, it is conceivable that an appropriately designed, non-peptide helix should be capable of these same activities. As previously described (Section 1.6.2), peptoids have been shown to form remarkably stable hehces, with physical characterishcs similar to those of peptide polyprohne type-I hehces (e.g. cis-amide bonds, three residues per helical turn, and 6A pitch). A faciaUy amphipathic peptoid helix design, based on the magainin structural motif, would therefore incorporate cationic residues, hydrophobic aromatic residues, and hydrophobic aliphathic residues with threefold sequence periodicity. 

UV resonance Raman spectroscopy (UVRR), Sec. 6.1, has been used to determine the secondary structure of proteins. The strong conformational frequency and cross section dependence of the amide bands indicate that they are sensitive monitors of protein secondary structure. Excitation of the amide bands below 210 nm makes it possible to selectively study the secondary structure, while excitation between 210 and 240 nm selectively enhances aromatic amino acid bands (investigation of tyrosine and tryptophan environments) (Song and Asher, 1989 Wang et al., 1989, Su et al., 1991). Quantitative analysis of the UVRR spectra of a range of proteins showed a linear relation between the non-helical content and a newly characterized amide vibration referred to as amide S, which is found at 1385 cm (Wang et al., 1991). 

Based on the backbone-rigidification strategy, oligomers with sufficiently long (> 7 subunits) backbones should adopt helical conformations in which one end of the molecule lies above the other. Extensive NOESY studies on the symmetrical nonamer 4 confirmed this expectation [50]. In addition to the presence of numerous well-resolved amide-side chain NOEs, the NOESY spectrum of 4 also revealed an end-to-end NOE cross peak between the end methyl (Me) protons and aromatic proton b 1 (Fig. 7). Due to the symmetrical... 

Hue et al. reported aromatic oligoamides based on quinoline residues (Fig. 24a) [65]. It was found that the corresponding oligomers folded into stable helical conformations based on three-center intramolecular hydrogenbonding interactions involving the amide protons and their adjacent pyridine N atoms. This class of oligomers was found to be stably folded in both nonpolar and polar solvents. Their folded conformations were also revealed by their crystal structures. 

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