Aromatic hypothesis

The Aromatic Hypothesis. In addition to the specifically conserved tryptophan residues, we had previously noted that the squalene-hopene cyclase and the oxidosqualene-lanosterol cyclase are generally rich in both tprptophan and tyrosine, amino acid residues with electron-rich aromatic sidechains (42), The squ ene-hopene cyclase contains 3.2% tryptophan and 4.0% tyrosine. The median values for representation of these amino acids in E, coli proteins are 1.2% and 2.7%, respectively (43). The levels of tryptophan and tyrosine found in the B. acidocaldarius enzyme exceed those found in > 95% and 85% of E, coli proteins, respectively. The oxidosqualene-lanosterol cyclase contains 3.0% ti tophan and 6.3% tyrosine. When compared to proteins from the yeast S. cerevisiae (for which the me an values for representation of tryptophan and tyrosine are 0.9% and 3.3%, respectively), the C. albicans enzyme i ssesses these amino acids at levels greater than those found in 99% of all S. cerevisiae proteins. 

We intend to test the aromatic hypothesis through detailed structure/function analyses of cyclase enzymes. We have developed a heterologous expression system for tile C. albicans cyclase, and are beginning studies directed at determining the effects of both directed and random mutations on the activity and product specificity of this enzyme. 

In this chapter I have attempted to collect all the data available on the photoisomerization reactions of pentaatomic aromatic heterocycles. At the end of this work, I can note that all the results fit the hypothesis I reported in the introduction of this chapter. 

This statement does not mean, however, that the mechanism of diazotization was completely elucidated with that breakthrough. More recently it was possible to test the hypothesis that, in the reaction between the nitrosyl ion and an aromatic amine, a radical cation and the nitric oxide radical (NO ) are first formed by a one-electron transfer from the amine to NO+. Stability considerations imply that such a primary step is feasible, because NO is a stable radical and an aromatic amine will form a radical cation relatively easily, especially if electron-donating substituents are present. As discussed briefly in Section 2.6, Morkovnik et al. (1988) found that the radical cations of 4-dimethylamino- and 4-7V-morpholinoaniline form the corresponding diazonium ions with the nitric oxide radical (Scheme 2-39). 

First we will discuss reaction systems of the types shown here in which adducts were detected analytically and characterized as 7T-complexes. The idea of 7T-com-plexes as intermediates on the path to products of an electrophilic aromatic substitution was originally suggested by Dewar (1949). He did not, however, follow his hypothesis further. It was taken up again by Olah, particularly in relation to nitration (reviews Olah, 1971 Olah et al., 1987, 1989). 

Thomae, A. V., Wunderli-Allenspach, H., Kramer, S. D. Permeation of aromatic carboxylic adds across lipid bilayers the pH-partition hypothesis revisited. Biophys. J. 2005, 89,1802-1811. 

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