Sequence features

Scheme 33 Oltra s and Cuerva s tandem sequence featuring a 7-endo cyclization...

It has been shown that Lewis acid catalyzed isomerization of thionolactones provides access to thiolactones. For example, exposure of the substrate 22 to catalytic amounts of BF3 OEt2 led to efficient conversion to the thiolactone 23. Such transformations were also found to give minor amounts of lactone or dithiolactone side products <06TL6067>. Substituted tetrahydrothiophene derivatives have also been obtained from 1,4-dithiane-2,5-diol and 2-nitroethyl acetate derivatives by a base induced sequence featuring a Michael addition and a Henry reaction <06TL8087>. 

The mechanism for the addition of singlet carbenes to alcohols has been studied in some detail (Bethell et al, 1971 Kirmse et al, 1981). By and large, the evidence supports two routes. The first, more common, sequence features initial formation of an ylid. Under some circumstances this reaction is reversible (Zupancic et al., 1985 Liu and Subramanian, 1984 Warner and Chu, 1984). Next, proton transfer, either intramolecularly, which may be slowed by symmetry constraints, or by a pair of intermolecular protonation and deprotonation steps, gives the ether. These reactions are outlined in (7). 

Karlin, S., and Altschul, S. F. (1990). Methods for assessing the statistical significance of molecular sequence features by using general scoring schemes. Proc. Natl. Acad. Sci. U.S.A. 87, 2264-2268. 

In recent years, a surprise in the study of signal peptides has been that signal peptides can be recognized by different factors, and the differences of their sequence features determine the preferences to these factors (Zheng and Gierasch, 1996 Siegel, 1995). 

The sequence features of presequences are well known typically they are from 20 to 80 residues long preferably contain basic residues, serine,... 

Claros (1995) released an attractive program, MitoProt. In this program, various sequence features of a potential signal region are reported to assist in the user s decision making. Later, an objective prediction method that combines many sequence features by the discriminant analysis was proposed (Claros and Vincens, 1996). With a cross-validation test, its accuracy was estimated to be 75%. 

Despite these problems EST databases are a valuable source of large-scale analysis of human variation. They will become even more valuable as the data continue to grow at the present rate. An algorithm for computer-aided SNP mining should contain filters to eliminate the potential sequence errors. Such filters can be based on the probabilistic analysis of sequence features. It can also take into account that multiple occurrences of a variant are more trustworthy, and it may furthermore focus on improving the quality of base-calling if the fluorescent traces are available for closer srcutiny. 

Fig. 19. Sequence features of the Rieske-type Fe S proteins. C, Cysteine D, aspartic acid F, phenylalanine G, glycine H, histidine I, isoleucine L, leucine P, proline S, serine T, threonine V, valine, W, tryptophan Y, tyrosine.

The assignment of (/ )-2,3-dihydro-2-phenylfuran rests on Jones oxidation which furnished (ft)-dihydro-5-phenyl-2(3//)-furanone [(/ )-24]80. The configuration of the corresponding S-enantiomer (obtained by yeast reduction of 4-oxo-4-phenylbutanoic acid) was established by correlation with ethyl (S)-3-hydroxy-3-phenylpropanoate (of known configuration, obtained itself by a baker s yeast reduction) by a sequence featuring an Arndt -Eistert homologization as the key step (see also p 403)19. 

RNA polymerase I (Pol I) is responsible for the synthesis of only one type of RNA, a transcript called pre-ribosomal RNA (or pre-rRNA), which contains the precursor for the 18S, 5.8S, and 28S rRNAs (see Fig. 26-22). Pol I promoters vary greatly in sequence from one species to another. The principal function of RNA polymerase II (Pol II) is synthesis of mRNAs and some specialized RNAs. This enzyme can recognize thousands of promoters that vary greatly in sequence. Many Pol II promoters have a few sequence features in common, including a TATA box (eukaryotic consensus sequence TATAAA) near base pair —30 and an Inr sequence (initiator) near the RNA start site at +1 (Fig. 26-8). 

Critical sequence features of an RNA aptamer that binds ATP are shown in Figure 2 molecules with this general structure bind ATP (and other adenosine nucleotides) with Kd < 50 /xm. Figure 3 presents the three-dimensional structure of a 36 nucleotide RNA aptamer (shown as a complex with AMP) generated by SELEX. This RNA has the backbone structure shown in Figure 2. 

The initial conceptualization of the agelastatin A problem took on the form shown below (Scheme 5).17 The key transform in this sequence features intramolecular addition of an amide-derived anion to a tethered alkynyliodonium salt within 33. The alkylidenecarbene generated from this nucleophilic addition, 32, then has a choice of two diastereotopic C-H bonds (Ha or Hb) for 1,5 insertion. Reaction with Ha would provide an advanced intermediate 31 en route to the target 28. Successful execution of this plan would extend alkynyliodonium salt chemistry in three new directions (1) use of an amine derivative as a nucleophile, (2) intramolecularity in the nucleophile addition step, and (3) diastereoselectivity upon alkylidenecarbene C-H insertion. At the initiation of this project, a lack of precedent on any of these topics suggested that focused scouting experiments to assess feasibility would be prudent before beginning work towards the natural product itself. 

Table 2 Key Sequence Features of Ketone Reductases and Conservations by S. cerevisiae Open Reading Frames... 

The direct sequence encoding methods preserve the order of residues along the sequence string and encode primarily local information. They are, however, not suitable when global sequence features or information content is more important to the application, or when variable length sequences are to be analyzed. This is evident in the intron/exon sequence discrimination (e.g., Uberbacher Mural, 1991 Snyder Stormo, 1993) and protein classification (e.g., Wu et al., 1992 Ferran Ferrara, 1992) problems. 

Other sequence features and information content can be extracted by various scoring mechanisms (e.g., Uberbacher et al1996). Another example of indirect sequence encoding is the computation of hydrophobic moment (Chapter 6.4). 

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