Covalent Bonding in Peptides

A second kind of covalent bonding in peptides occurs when a disulfide linkage, RS-SR, is formed between two cysteine residues. As we saiv in Section 18.8, a disulfide is formed by mild oxidation of a thiol, RSH, and is cleaved by mild reduction. 

The peptide linkage is usually portrayed by a single bond between the carbonyl carbon and the amide nitrogen (Figure 5.3a). Therefore, in principle, rotation may occur about any covalent bond in the polypeptide backbone because all three kinds of bonds (N——C, and the —N peptide bond) are sin-... 

The nature of the covalent bonds in the polypeptide backbone places constraints on structure. The peptide bond has a partial doublebond character that keeps the entire six-atom peptide group in a rigid planar configuration. The N—C and Ca—C bonds can rotate to assume bond angles of (p and ip, respectively. 

Another type of covalent bond in proteins is the disulfide bond, formed by oxidative coupling of the -SH groups in cysteine. Oxytocin is an example of a cyclic peptide with a S-S bond. 

The structure of both peptides includes a disulfide bond, a form of covalent bonding in which the - SH groups from two cysteine residues are oxidized to form a sulfur-sulfur bond. In oxytocin and vasopressin, the disulfide bonds make the peptides cyclic. Three-dimensional structures of oxytocin and vasopressin are shown in Figure 28.7. 

The isoelectric point for histidine is the pH value halfway between the pK values for the two nitrogen-containing groups. The p.Aa and pi values of amino acids in peptides and proteins differ somewhat from those of free amino acids, principally because most of the a-amino and a-carboxyl groups are not ionized but are covalently joined in peptide bonds. 

Which of the following shows the linear sequence of atoms joined by covalent bonds in a peptide backbone ... 

Hydrolases catalyze the hydrolytic splitting of covalent bonds ester, peptide, acid anhydride, etc. Table 2 contains data on hydrolases which have been utilized in research on bioelectrocatalysis. 

The enzymes used to create ELP hydrogels in a biocompatible process is transglutaminase (tTG] (Bozzini etal., 2011]. The enzyme catalyzes the calcium-dependent acyl transfer reaction that results in the formation of a y-glutamyl- -lysyl covalent bond between peptide-bound glutamine residues and various primary amines. 

By changing Ser 221 in subtilisin to Ala the reaction rate (both kcat and kcat/Km) is reduced by a factor of about 10 compared with the wild-type enzyme. The Km value and, by inference, the initial binding of substrate are essentially unchanged. This mutation prevents formation of the covalent bond with the substrate and therefore abolishes the reaction mechanism outlined in Figure 11.5. When the Ser 221 to Ala mutant is further mutated by changes of His 64 to Ala or Asp 32 to Ala or both, as expected there is no effect on the catalytic reaction rate, since the reaction mechanism that involves the catalytic triad is no longer in operation. However, the enzyme still has an appreciable catalytic effect peptide hydrolysis is still about 10 -10 times the nonenzymatic rate. Whatever the reaction mechanism... 

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