Amides structural motifs

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. 

Scheme 3.6-1. Structural motifs of main group metal amides, phosphanides and arsanides (E = N, P, As).

The intervening years have seen huge growth in the number of well-characterized compounds, the vast majority of which are lithium, sodium or potassium salts. Their strucuiral chemistry has proven to be especially rich and the number of structures of alkali metal amides currently available exceeds 200. These involve a wide selection of structural motifs that were mostly unknown in 1980. 

The dimeric (LiN)2 structural motif (discussed in Section 2.2.3) is of central importance in a mode of lithium amide association known as laddering (Structure C). The phenomenon was first described by Snaith and co-workers with the structure... 

Vibrational spectroscopy has been used in the past as an indicator of protein structural motifs. Most of the work utilized IR spectroscopy (see, for example, Refs. 118-128), but Raman spectroscopy has also been demonstrated to be extremely useful (129,130). Amide modes are vibrational eigenmodes localized on the peptide backbone, whose frequencies and intensities are related to the structure of the protein. The protein secondary structures must be the main factors determining the force fields and hence the spectra of the amide bands. In particular the amide I band (1600-1700 cm-1), which mainly involves the C=0-stretching motion of the peptide backbone, is ideal for infrared spectroscopy since it has an large transition dipole moment and is spectrally isolated... 

Coherent transport of vibrational energy is further limited by vibrational energy relaxation. Experiments on the amide I band of different peptides (NMA, apamin, scyllatoxin BPTI, and the cyclic pentapeptide) revealed a vibrational relaxation rate of approximately Ti = 1.2 ps, which is essentially independent of the particular peptide (30,53). A similar value has recently been reported for myoglobin at room temperature, with only a weak dependence of the relaxation rate on temperature down to cryogenic temperatures (140). In other words, vibrational relaxation of the amide I mode reflects an intrinsic property of the peptide group itself rather than a specific characteristic of the primary or secondary structural motifs of the... 

SCHEME 1. Common structural motifs of lithium amides... 

In summary, chelating chiral lithium amides exist in either of four major structural motifs or mixtures of them (Scheme 3). Non-coordinating solvents generally favor cyclic trimers, A. Ladder tetramers are favored for pyrrolidide amides in the absence of coordinating solvents. 

The ladder structures found in 5-block amides are common structural motifs in phosphides as well. Solvent free [LiP(SiMe3)2]6 displays such an arrangement in the solid state, with four five-coordinate and two four-coordinate P atoms and four three-coordinate and two two-coordinate Li atoms the Li—P distances range from 2.38 A to 2.63 A (see Figure 52)." Li4(/X2-PR2)20 3 PR2)2(TFIF)2, formed from the reaction of P(SiMe3)3 with Bu Li in TFIF, has a fused tricyclic (LiP)4 ladder skeleton. The Li atoms are three-coordinate, with each of the two terminal lithiums bound to two P atoms and one THF, while the two internal lithiums have three phosphorus atoms as neighbors (see Figure 53)." " In solution, there is no NMR evidence for Xi- P... 

Amides frequently combine two unique structural motifs, dimers and catemers, into a well-known 1-D ribbon-like structure. The dimer is constructed from self-complementary N-H O hydrogen bonds, while the catemeric N-H O hydrogen bonds result from the anti-proton of the amine and the bifurcated carbonyl oxygen atom. 

Zinc enzymes catalyze the hydrolysis of amide bonds using a variety of active site structural motifs.77 An extensively studied enzyme of this class is carboxypeptidase A, which contains a mononuclear zinc center (Fig. 13) within the enzyme active site and catalyzes the hydrolysis of a C-terminal amino acid.78,79 The mechanism of amide cleavage in carboxypeptidase A has been studied extensively.77,78 In one proposed mechanistic pathway for this enzyme (Scheme 13), termed the zinc hydroxide mechanism , the zinc center activates a water molecule for deprotonation and also assists in polarization of the substrate carbonyl moiety, thus making it more susceptible to nucleophilic attack. The zinc center also provides transition state stabilization through charge neutralization. 

Figure 7.17. Molecular structure of a peptide fragment characterized by a retro-inverso amide bond motif.

Structural keys describe the chemical composition and eventually structural motifs of molecules represented as a boolean array. If a certain structural feature is present in a molecule or a substructure, a particular bit is set to 1 (true) and otherwise to 0 (false). A bit in this array may encode a particular functional group (such as a carboxylic acid or an amid linkage), a structural element (e.g. a substituted cyclohexane), or at least n occurrences of a particular element (e.g. a nitrogen atom). Alternatively, the structural key can be defined as an array of integers, where the elements of this array contain the frequency of how often a specific feature occurs in the molecule. 

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