Tryptophan models

A number of studies on the fluorescence decay of tyrosine, tyrosine derivatives, and small tyrosyl peptides have been carried out. 36-38 Whereas the tyrosine zwitterion and tyrosine derivatives with an ionized a-carboxy group exhibited monoexponential fluorescence decay (x = 3.26-3.76 ns), double- or triple-exponential decay was observed in most other cases. As in the case of the tryptophan model compounds, the complex decay kinetics were again interpreted in terms of rotamer populations resulting from rotation around the C —Cp bond. There is evidence to indicate that the shorter fluorescence lifetimes may arise from rotamers in which the phenol ring is in close contact with a hydrated carbonyl group 36 37 and that a charge-transfer mechanism may be implicated in this quenching process. 39 ... 

Martens and Naes discuss the topic and several definitions are quoted in the literature. In a simple example we can express leverage, h, as the diagonal elements of the matrix (Z-Z ), where Z is the matrix of factors in the two-factor PLS tryptophan model. In this case,... 

Sokolovsky et al. 368) studied the reaction of TNM with amino acids other than tyrosine and found that cysteine, methionine, histidine and tryptophan could be modified by the reagent. By using tryptophan model compounds, it was demonstrated that a number of nitrated derivatives of tryptophan of unknown structure could be obtained. 

Measuring Protein Sta.bihty, Protein stabihty is usually measured quantitatively as the difference in free energy between the folded and unfolded states of the protein. These states are most commonly measured using spectroscopic techniques, such as circular dichroic spectroscopy, fluorescence (generally tryptophan fluorescence) spectroscopy, nmr spectroscopy, and absorbance spectroscopy (10). For most monomeric proteins, the two-state model of protein folding can be invoked. This model states that under equihbrium conditions, the vast majority of the protein molecules in a solution exist in either the folded (native) or unfolded (denatured) state. Any kinetic intermediates that might exist on the pathway between folded and unfolded states do not accumulate to any significant extent under equihbrium conditions (39). In other words, under any set of solution conditions, at equihbrium the entire population of protein molecules can be accounted for by the mole fraction of denatured protein, and the mole fraction of native protein,, ie. 

The second line of circumstantial evidence quoted in support of this hypothesis is the ready formation of l,2,3,4-tetrahydro-/3-carboline derivatives under pseudo-physiological conditions of temperature, pH, and concentration. Tryptamine and aldehydes, trypt-amine and a-keto acids, and tryptophan and aldehydes condense at room temperature in a Pictet-Spengler type intramolecular Mannich reaction in the pH range 5.2-8.0 (cf. Section III, A, 1, a). It was argued that experiments of this type serve as models for biochemical reactions and may be used in evidence. 

In contrast to the wealth of biogenetic speculation and model experimentation, none of which has direct bearing on actual biochemical events in the synthesis of /3-carbolines in their natural habitat, very few biosynthetic investigations have been carried out. As predicted, radioactivity from 2- C-tryptophan was incorporated into carbon atom-3 of the 1,2,3,4,4a,9a-hexahydro-)3-carboline moiety of ajmaUne and into carbon atom-3 of the jS-carbohnium segment... 

In an attempt to visualize the site of action of ethanol, tryptophan mutation at position S270, TM2 and TM3 domains of the GABAa a2 subunit were modeled as antiparallel a-helices. The model showed that the region between S270 TM2 and TM3 contains a small cavity that may not be filled by side chains of adjoining helices. In contrast, the model of the S270W mutation demonstrated that the side chain of tryptophan completely occupied this cavity, which could eliminate occupation of the putative cavity by ethanol. 

To compare the disassembly rate of the above dendritic systems, we synthesized AB3 molecules 18 and 19 (Fig. 5.10). Both the molecules are designed for activation by PGA and have three units of tryptophan as a model drug. Tryptophan was used for initial evaluation as it contains a strong UV chromophore, allowing us to monitor the disassembly reaction. 

D-Gal — hydroxy-L-histidine,4950 d-G1cA — hydroxy-L-tryptophan,51 d-GlcA — hydroxy-L-phenylalanine,51 d-G1cA — L-Ser,51 and carbohydrates N-glycosylated to the a-amino group of the N-terminal portion of proteins.51-53 Most of these compounds will be discussed in more depth later in this article, in terms of model compounds for oligosaccharide linkages to proteins. 

Rachel, K., Asuncionpunzalan, E. and London, E. (1995) Anchoring of tryptophan and tyrosine analogs at the hydrocarbon polar boundary in model membrane-vesicles - paralax analysis of fluorescence quenching induced by nitroxide-labelled phospholipids. Biochemistry 34,15475-15479. 

Jensen, G. M., D. B. Goodlin, and S. W. Bunte. 1996. Density Functional and MP2 Calculations of Spin Densities of Oxidized 3-Methylindole Models for Tryptophan Radicals. J. Phys. Chem. 100, 954. 

Singhal, N. Snow, C. D. Pande, V. S., Using path sampling to build better Markovian state models predicting the folding rate and mechanism of a tryptophan zipper beta hairpin, J. Chem. Phys. Jul 2004,121, 415—425. 

There is always interest in the photochemistry of the pyrimidine nucleic acid bases and related simple pyrimidinones, due to its importance in genetic mutation. In addition to damaging DNA, photo-induced reactions may also repair the damage, as in the reduction, by FADH, of the thymine glycol 64 back to thymine <06JACS10934>. Another report related to repair of DNA involved a model study, by means of the linked dimer 65, of the involvement of tryptophan in the electron-transfer leading to reversion of thymine oxetane adducts <06OBC291>. 

S. S. Lehrer, Solute perturbation of protein fluorescence. The quenching of other tryptophan fluorescence of model compounds and of lysosome by iodide ion, Biochemistry 10, 3254-3263 (1971). 

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