Lysine ionizable side chain

The most significant amino acids for modification and conjugation purposes are the ones containing ionizable side chains aspartic acid, glutamic acid, lysine, arginine, cysteine, histidine, and tyrosine (Figure 1.6). In their unprotonated state, each of these side chains can be potent nucleophiles to engage in addition reactions (see the discussion on nucleophilicity below). 

Seven of the 20 amino acids have readily ionizable side chains. These 7 amino acids are able to donate or accept protons to facilitate reactions as well as to form ionic bonds. Table 3.1 gives equilibria and typical pi( values for ionization of the side chains of tyrosine, cysteine, arginine, lysine, histidine, and aspartic and glutamic acids in proteins. Two other groups in proteins—the terminal a-amino group and the terminal a- carboxyl group—can be ionized, and typical pi( ... 

The answer is b. (klurray, pp 27-36. Scriver, pp 3-45. Sack, pp 1-3. Wilson, pp 101-120.1 Except for terminal amino acids, all a-amino groups and all a-carboxyl groups are utilized in peptide bonds. Thus only amino acids with side chains may be considered. Of these, 7 of the 20 common amino acids have easily ionizable side chains. These arc the basic amino acids lysine, arginine, and histidine the acidic amino acids aspartate and glutamate and tyrosine and cysteine. Leucine, valine, and alanine have hydrocarbon side chains. 

Refer to Table 5.2 for the p fa values for lysine and aspartic acid, both of which have ionizable side chains. Lysine also contains a terminal a-amino and alanine a terminal a-carboxyl group. These values are as follows ... 

Some amino acids have additional ionizable groups in their side-chains. These may be acidic or potentially acidic (aspartic acid, glutamic acid, tyrosine, cysteine), or basic (lysine, arginine, histidine). We use the term potentially acidic to describe the phenol and thiol groups of tyrosine and cysteine respectively under physiological conditions, these groups are unlikely to be ionized. It is relatively easy to calculate the amount of ionization at a particular pH, and to justify that latter statement. 

Similar calculations as above for the basic side-chain groups of arginine pK 12.48) and lysine pK 10.52), and the acidic side-chains of aspartic acid (pATa 3.65) and glutamic acid (pAfa 4.25) show essentially complete ionization at pH 7.0. However, for cysteine (pATa of the thiol group 10.29) and for tyrosine (pAfa of the phenol group 10.06) there will be negligible ionization at pH 7.0. 

The amino acids in question are the basic amino acids lysine, arginine, and histidine, and the acidic amino acids aspartic acid and glutamic acid. The side-chain functions of these amino acids, ionized at pH 7 (see Box 4.7), act as acids or bases. In a reverse sequence, protons may be acquired or donated to regenerate the conjugate acids and conjugate bases. 

The exact ionic state of the side chains in the last two classes will depend on the pH of the solution. At pH 7.0 the side chains of glutamate and aspartate have ionized carboxylates, and the side chains of lysine and arginine have positively... 

The side chains of the basic amino acids accept protons (see Hgure 1.3). At physiologic pH the side chains of lysine and arginine are fully ionized and positively charged. In contrast, histidine is weakly basic,... 

An additional point should be noted from table 3.3. Whereas the amino acid side chains (R groups) that are normally charged at physiological pH are restricted to five amino acids (aspartic acid, glutamic acid, lysine, arginine, and sometimes histidine), a number of potentially ionizable R groups are part of other amino acids. These include cysteine, serine, threonine, and tyrosine. The ionization reac-... 

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