Tryptophan structural reporter

Typically, neurotoxic effects of drugs on monoamine neurons have been assessed from reductions in brain levels of monoamines and their metabolites, decreases in the maximal activity of synthetic enzymes activity, and decreases in the active uptake carrier. In the present study, the traditional markers described above have been used, including the measurement of the content of monoamines and their metabolites in brain at several different timepoints following drug administration. Since reports in the literature have documented that MDMA and MDA can inhibit the activity of tryptophan hydroxylase (TPH), the rate-limiting enzyme in serotonin synthesis (Stone et al. 1986 Stone et al. 1987). it is unclear whether MDMA-induced reductions in the content of serotonin and its metabolite 5-hydroxyin-doleacetic acid (5-HlAA) may be due to suppressed neurotransmission in otherwise structurally intact serotonin neurons or may represent the eonsequenee of the destruction of serotonin neurons and terminals. 

Structurally related quinoxalines have been identified as sub-micromolar HCV polymerase inhibitors in a high throughput screen (HTS). Derivatives that are unsymmetrically substituted with hydrophobic groups on the pyrazine moiety, and with a pendant hydroxy-tryptophan side-chain that has been reported previously (vide infra), provide the greatest activity (14, IC50 = 0.6 pM) [56]. 

Helical heptad repeat sequences have been reported to be well behaved although they are difficult to characterize by NMR spectroscopy due to spectral overlap. The motifs that have been shown to have native-like properties, and are not highly repetitive, have cores composed of aromatic amino acid side chains of, for example, phenylalanine and tryptophan. In four-helix bundle motifs [1, 2], the /1/la-motif BBAl [5] and the /1-sheet protein Betanova [9], the formation of the folded structure appears to be strongly dependent on such residues although the energetics have not been calculated by substitution studies. As a tentative rule, therefore, the probability of success in the design of a new protein is probably much higher if residues are included that can form aromatic clusters in the core (Fig. 5). 

A number of investigators have studied the effect of ozone on the ultraviolet absorption spectra of proteins and amino acids. A decrease in the absorption of 280-nm light in a number of proteins was originally reported ly Giese et aV to be a consequence of ozone exposure they suggested that this was due to an interaction of ozone with the ring structures of tyrosine and tryptophan. Exposure of a solution of tryptophan to ozone resulted in a decrease in 280-nm absorption, whereas the extinction coefficient of tyrosine increased. Similar results with tyrosine were reported by Scheel et who also noted alterations in the ultraviolet spectra of egg albumen, perhaps representing denaturation by ozone. 

One of the most interesting features of natural fluorescence results from the fact that the fluorescence response of a given molecule depends very much on their microenvironment. This feature can be used in order to gather information about the structure of complex molecules such as polypeptides and proteins, which may integrate several fluorescent amino acids residues such as tryptophan, tyrosine, and phenylalanine. Among these, tryptophan is the one that exhibits the highest quantum yield, which makes it a good candidate to be used as an intrinsic fluorescence reporter. 

Oxidation has been reported to occur with a number of compounds which contain nitrogen but possess no a-amino-alcohol structure.11 13 14 Thus, cystine, methionine, and tryptophan are oxidized, though without... 

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