Tyrosine replacement

The S3 pocket offers a shallow cavity to bind the conserved proline. The proline residue of the substrate would lie between the side chains of His 183, Phe 185, and Serl72 [36]. Residues 183 and 185 are conserved among the MMPs with the minor exception of a tyrosine replacing phenylalanine 164 in stromelysin. Residue 172 shows some variability among the MMPs existing as a serine in HNC and HFC and a tyrosine in the remainder of the aligned MMPs. 

It was therefore particularly inteipesting to investiage whether it would be possible to replace BPA by various derivatives of L-tyrosine as monomeric building blocks for the synthesis of poly-(iminocarbonates). In order to be practically useful in drug delivery applications, the replacement of BPA by derivatives of tyrosine must give rise to mechanically strong yet fully biocompatible polymers. 

In a related series of experiments, the amino group and/or the carboxylic acid group of tyrosine were replaced by hydrogen atoms. The corresponding tyrosine derivatives are 3-(4 -hydroxyphenyl)-propionic acid, commonly known as desaminotyrosine (Dat), and tyramine (Tym) (structures 3-5). 

In hemoglobin M, histidine F8 (His F8) has been replaced by tyrosine. The iron of HbM forms a tight ionic complex with the phenolate anion of tyrosine that stabilizes the Fc3 form. In a-chain hemoglobin M variants, the R-T equilibrium favors the T state. Oxygen affinity is reduced, and the Bohr effect is absent. P Ghain hemoglobin M variants exhibit R-T switching, and the Bohr effect is therefore present. 

Humans can synthesize 12 of the 20 common amino acids from the amphiboHc intermediates of glycolysis and of the citric acid cycle (Table 28-1). While nutritionally nonessenrial, these 12 amino acids are not nonessential. AH 20 amino acids are biologically essential. Of the 12 nutritionally nonessential amino acids, nine are formed from amphibolic intermediates and three (cysteine, tyrosine and hydroxylysine) from nutritionally essential amino acids. Identification of the twelve amino acids that humans can synthesize rested primarily on data derived from feeding diets in which purified amino acids replaced protein. This chapter considers only the biosynthesis of the twelve amino acids that are synthesized in human tissues, not the other eight that are synthesized by plants. 

Tyrosine. Phenylalanine hydroxylase converts phenylalanine to tyrosine (Figure 28-10). Provided that the diet contains adequate nutritionally essential phenylalanine, tyrosine is nutritionally nonessential. But since the reaction is irreversible, dietary tyrosine cannot replace phenylalanine. Catalysis by this mixed-function oxygenase incorporates one atom of O2 into phenylalanine and reduces the other atom to water. Reducing power, provided as tetrahydrobiopterin, derives ultimately from NADPH. 

The strategy of introducing non-natural aminoacids into the oxytocin peptide skeleton in order to make antagonists has also been exploited by Havaas et al. [51], who replaced the proline at the 7-position with sarcosine and modified the tyrosine residue at the 2-position to introduce further conformational constraint. A representative example is shown, (13), with a... 

In an attempt to identify more biocompatible diphenols for the design of degradable biomaterials, we studied derivatives of tyrosine dipeptide as potential monomers. After protection of the amino terminus and the carboxylic acid terminus, the reactivity of tyrosine dipeptide (Figure 1) could be expected to be similar to the reactivity of industrial diphenols. Thus, derivatives of tyrosine dipeptide could be suitable replacements for BPA in the synthesis of a variety of new polymers that had heretofore not been accessible as biomaterials due to the lack of diphenolic monomers with good biocompatibility. 

Endomorphin-2 (Tyr-Pro-Phe-NH ), a potent and selective MOR agonist, was used as a template for MOR antagonist design [54,55]. Replacing the N-terminal tyrosine residue with 2,6-dimethyltyrosine... 

The ability of MPO to catalyze the nitration of tyrosine and tyrosyl residues in proteins has been shown in several studies [241-243]. However, nitrite is a relatively poor nitrating agent, as evident from kinetic studies. Burner et al. [244] measured the rate constants for Reactions (24) and (25) (Table 22.2) and found out that although the oxidation of nitrite by Compound I (Reaction (24)) is a relatively rapid process at physiological pH, the oxidation by Compound II is too slow. Nitrite is a poor substrate for MPO, at the same time, is an efficient inhibitor of its chlorination activity by reducing MPO to inactive Complex II [245]. However, the efficiency of MPO-catalyzing nitration sharply increases in the presence of free tyrosine. It has been suggested [245] that in this case the relatively slow Reaction (26) (k26 = 3.2 x 105 1 mol-1 s 1 [246]) is replaced by rapid reactions of Compounds I and II with tyrosine, which accompanied by the rapid recombination of tyrosyl and N02 radicals with a k2i equal to 3 x 1091 mol-1 s-1 [246]. 

Consider one small molecule, phenylalanine. It is an essential amino acid in our diet and is important in protein synthesis (a component of protein), as well as a precursor to tyrosine and neurotransmitters. Phenylalanine is one of several amino acids that are measured in a variety of clinical methods, which include immunoassay, fluorometry, high performance liquid chromatography (HPLC see Section 4.1.2) and most recently MS/MS (see Chapter 3). Historically, screening labs utilized immunoassays or fluorimetric analysis. Diagnostic metabolic labs used the amino acid analyzer, which was a form of HPLC. Most recently, the tandem mass spectrometer has been used extensively in screening labs to analyze amino acids or in diagnostic labs as a universal detector for GC and LC techniques. Why did MS/MS replace older technological systems The answer to this question lies in the power of mass spectrometer. 

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