Cyclic structural motifs

Upon mutagenesis of the monoamine oxidase from Aspergillus niger (MAO-N) within several rounds of directed evolution [65], variant biocatalysts were identified with largely expanded substrate acceptance, enabling also the deracemization of tertiary amines incorporating straight-chain and cyclic structural motifs [66]. 

A quite different structural motif is found in the curious cyclic hexamer [(BNMc2)6] which can be obtained as orange-red crystals by distilling the initial product formed by dehalogenation of (Me2N)2BCl with Na/K alloy ( >... 

Many peptide antibiotics have novel structural motifs, such as cyclic structures and are often further modified, (such as in jS-lactamic antibiotics) and conjugated with sugars, lipids, and other molecules. 

In this short section, cyclic compounds are discussed that are not strictly lactones since they contain an endocyclic structural motif of the type -O-CO-X- or -X-O-CO-. However, these compounds share with lactones the possibility to be hydrolyzed at the endocyclic -CO-O- bond. This is the case for cyclic diesters of carbonic acid (-O-CO-O-), cyclic esters of car-bamic acid (-0-C0-NH-), and cyclic anhydrides (-C0-0-C0-). One example of each class is presented here. 

The widespread occurrence of cyclic peptides and depsipeptides in natura makes the research on the development of rapid and efficient approaches for their generation mandatory. The rational design of synthetic cycfic peptide analogs, focused on biological activities that imitate natural structural motifs (turns, hefices, etc.), can help to increase their native properties and to adapted them for human applications, for example, in medicine [12-14]. 

Peptides with a motif that favor a cyclic structure are recommended in this approach. Two peptides derived from the V3 loop of the surface protein gpl20 of human immunodeficiency virus, GPGRAFYTTKNIIG and KRKRIHIGPGRAFYTTKNIIG, are used to illustrate this example. Both peptides contain a turn motif, GPGR, in the middle of the sequence that may facilitate the ring-chain tautomerization in the cyclization process. 

Tetrahydropyrans bearing halides at C4 can be accessed by a modified Taddei-Ricci reaction. The reaction involves condensation of allyltrimethylsilane, aldehydes and a cyclic acetal 371 in the presence of a Lewis acid to afford all ry -tetrahydropyrans 372 as a single diastereomer. The reaction proceeds via anion mediated ring closure of oxonium ion intermediate 373 (Scheme 89). This methodology was successfully applied to the synthesis of a model compound bearing all the structural motifs present in the eastern subunit of okadaic acid <1997TL2895>. 

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... 

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 cooperative, infinite chains and cycles formed by O-H 0 hydrogen bonds in the a-cyclodextrin hydrates are a characteristic structural motif [109]. As with the simpler carbohydrate crystal structures described in Part II, Chapter 13, the hydrogen bonds can be traced from donor to acceptor in the cyclodextrin hydrate crystal structures. Networks of O-H 0-H 0-H interactions are observed in which the distribution of hydrogen bonds follows patterns with two characteristic motifs. One are the "infinite chains which run through the whole crystal lattice, and the others are the loops or cyclically closed patterns (a special case of the "infinite chains). As in the small molecule hydrates, such as a-maltose monohydrate, the chains and cycles are interconnected at the water molecules to form the complex three-dimensional networks illustrated schematically in Fig. 18.5, with some sections shown in more detail in Fig. 18.7 a, b, c. 

Applications of cyclised oligonucleotides are varied. They have been used to produce artificial human telomeres by rolling circle DNA synthesis/as inhibitors of viral replication in influenza virus and as structural motifs for quadruplex formation.A further form of cyclic oligonucleotide figures in a recently described method in which a self-complementary oligonucleotide, e.g., a hairpin structure, is denatured and allowed to re-anneal in the presence of circular DNA such as a plasmid (7). The effect is that the short oligonucleotide traps the plasmid in what has been termed a padlock. Such structures have been successfully used to inhibit transcription elongation reactions based on triple helix formation of the padlock structure. 

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