Dissociation constant of amino-acids

Table 1.10 Dissociation constants of amino acids at 25°C. (According to B. E. Conway)...

At low pH, both the ammonium group and the carboxyl group are protonated. At high pH, neither is protonated. Acid dissociation constants of amino acids are listed in Table 10-1, where each compound is drawn in its fully protonated form. 

Table 10-1 Acid dissociation constants of amino acids... 

Dissociation Constants of Amino-Acids.—A very considerable simplification in the treatment of amino-acids can be achieved by regarding them as dibasic acids. Consider, for example, the hydrochloride of glycine, i.e., C1"" +NH3CH2C02H when this is neutralized by an alkali hydroxide, there are two stages of the reaction, corresponding in principle to the two stages of neutralization of a dibasic acid, thus... 

As in Section 14.3.3, we shall deal only with the rapid equilibrium of substrate and hydrogen-ion binding, because the full steady-state equations are very complex. Hence, the Michaelis constant represents the true dissociation constant of respective enzyme-substrate complexes, and Kp and Kb represent the acid dissociation constants of amino acids in the free and the bound enzyme, respectively. 

The dissociation constants of amino acids can be determined, for example, by titration of the acid. Figure 1.2 shows titration curves for glycine, histidine and aspartic acid. Table 1.2 lists the dissociation constants for some amino acids. In amino acids the acidity of the carboxyl group is higher and the basicity of the amino group lower than in the corresponding carboxylic acids and amines (cf. pK values for propionic acid, 2-propylamine and alanine). As illustrated by the comparison of pK values of 2-aminopropionic acid (alanine) and 3-aminopropionic acid ( 3-alanine), the pK is influenced by the distance between the two functional groups. 

Table 9 includes data on the first dissociation constants of seven weak acids it will be recalled that we expect these to fall into class III. The table includes the second dissociation constants of five acids, phosphoric, sulfuric, oxalic, malonic, and carbonic, which fall into class IV, while the amino acids glycine and alanine provide four examples that should fall into class II. 

The pronounced electron-withdrawing nature of the 1,2,5-thiadiazole system is also evidenced by strong carbonyl electrophilic activation and by enhancement of carboxy acidity. The acid dissociation constants of thiadiazole acids, discussed in Section 4.09.4.1, fall in the range 1.5-2.5. The 1,2,3-thiadiazole carboxylic acids are easily decarboxylated at 160-200 °C. This reaction has been used for the synthesis of monosubstituted derivatives as well as the parent ring and deuterated derivatives <68AHC(9)107>. An efficient bromo-decarboxylation of 3-amino-1,2,5-thiadiazole-carboxylic acid has also been reported <70BRP1190359>. 

Solinova V., Kasicka V., Koval D., Cesnek M., Holy A., Determination of acid—base dissociation constants of amino- and guanidinopurine nucleotide analogs and related compounds by capillary zone electrophoresis. Electrophoresis, 27, 1006—1019 (2006). 

Himdin [8001-27-2] is a polypeptide of 66 amino acids found ia the saUvary gland secretions of the leech Himdo medicinalis (45). It is a potent inhibitor of thrombin and biads to y-thrombia with a dissociation constant of 0.8 x 10 ° M to 2.0 x lO " M. Himdin forms a stable noncovalent complex with free and bound thrombin completely iadependent of AT-III. This material has now been cloned and expressed ia yeast cells (46,47). Its antigenic poteatial ia humans remains to be estabUshed. 

Note that the dissociation constants of both the a-carboxyl and a-amino groups are affected by the presence of the other group. The adjacent a-amino group makes the a-COOH group more acidic (that is, it lowers the pAl, ) so... 

Different Types of Proton Transfers. Molecular Ions. The Electrostatic Energy. The ZwiUertons of Amino Acids. Aviopro-tolysis of the Solvent. The Dissociation Constant of a Weak Acid. Variation of the Equilibrium Constant with Temperature. Proton Transfers of Class I. Proton Transfers of Classes II, III, and IV. The Temperature at Which In Kx Passes through Its Maximum. Comparison between Theory and Experiment. A Chart of Occupied and Vacant Proton Levels. 

Amino acids are characterized by the presence of adjacent carboxylic (-C0 H) and amino (-NH) functional groups. The equilibrium constant for protonation or dissociation of these groups is a function of their position in the amino acid molecule. Therefore, widely differing acid-base properties of amino acids occur, depending upon the number of functional groups and their relative position in the molecule. The dissociation constants for various amino acids used in this investigation are given in Table I. 

When the R group contains another ionizable group, the amino acid will have more than two dissociation constants. The carboxylic acid gronps of aspartic acid and glutamic acid, the amine of lysine, and the guanidino group of arginine will all... 

Despite their very short sequence (7 to 38 amino acid residues for the 12 histatins identified so far), the histidine-rich salivary protein histatins have also been reported to precipitate tannins, eventually more efficiently than proline-rich proteins, especially at neutral pH and high tannin concentration. A detailed NMR analysis of the binding between EGCG and histatin 5, a 24-mer that is very rich in basic His, Lys, and Arg residues ( 60%) and devoid of secondary structure, has revealed noncooperative binding of six to seven flavanol molecules with a dissociation constant of 1 mM (pH 3.0, 25°C). ... 

Application of the Henderson-Hasselbalch equation The dissociation constant of the carboxyl group of an amino acid is called K1f rather than Ka, because the molecule contains a second titrat-able group. The Henderson-Hasselbalch equation can be used to analyze the dissociation of the carboxyl group of alanine in the same way as described for acetic acid. 

Shea and colleagues [109-111] added an exciting contribution to this field They created molecular imprints for the peptide melittin, the main component of bee venom, in polymer nanoparticles, resulting in artificial antibody mimics that can be used for the in vivo capture and neutralization of melittin. Melittin is a peptide comprising 26 amino acids which is toxic because of its cytolytic activity. Shea and colleagues strategy was to synthesize cross-linked, acrylamide-based MIP nanoparticles by a process based on precipitation polymerization using a small amount of surfactant. To maximize the specificity and the affinity for melittin, a number of hydrophilic monomers were screened for complementarity with the template. The imprinted nanoparticles were able to bind selectively the peptide with an apparent dissociation constant of Ax>app > 1 nM [109]. 

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