Peptides degradation reactions

Underlined sequences indicate amino acid sequences used for the generation of degenerate primers. Bracketed question marks represent blank cycles from the Edman degradation reaction. Additional sequence was obtained after blank cycles in all cases except the Glu-C-1 and Glu-C-2 peptides. 

Peptides can undergo a variety of degradation reactions (Fig. 6.4) [6-9], Pathways of physical degradation include aggregation, precipitation, and adsorption. Denaturation, i. e., an often-irreversible alteration of the tertiary structure of a peptide, is also considered a type of physical degradation. These physical reactions fall outside the scope of this work. 

Fig. 6.25. Simplified mechanism of two degradation reactions between peptides and reducing sugars occurring in solids, a) Maillard reaction between a side-chain amino (or amido) group showing the formation of an imine (Reaction a), followed by tautomerization to an enol (Reaction b) and ultimately to a ketone (Reaction c). Reaction c is known as the Amadori rearrangement (modified from [8]). b) Postulated mechanism of the reaction between a reducing sugar and a C-terminal serine. The postulated nucleophilic addition yields an hemiacetal (Reaction a) and is followed by cyclization (intramolecular condensation Reaction b). Two subsequent hydrolytic steps (Reactions c and d) yield a serine-sugar conjugate and the des-Ser-peptide...

Proteins are subject to a variety of chemical modification/degradation reactions, viz. deamidation, isomerization, hydrolysis, disulfide scrambling, beta-elimination, and oxidation. The principal hydrolytic mechanisms of degradation include peptide bond... 

In addition to deliberate enzyme-catalyzed processes, there are nonenzymatic processes that alter proteins. These include the degradative reactions described in Section 5 and also reversible reactions that may be physiologically important. For example, the N-terminal amino groups of peptides, and other amino groups of low p Ka can form carbamates with bicarbonate (Eq. 2-21 ).301-303 This provides an important mechanism of carbon dioxide transport in red blood cells (Chapter 7) and a way by which C02 pressure can control some metabolic processes. 

An initially surprising conclusion drawn from the studies of Schoenheimer and Rittenberg was that proteins within cells are in a continuous steady state of synthesis and degradation. The initial biosynthesis, the processing, oxidative and hydrolytic degradative reactions of peptides, and further catabolism of amino acids all combine to form a series of metabolic loops as discussed in Chapter 17 and dealt with further in Chapters 12 and 29. Within cells some proteins are degraded much more rapidly than others, an important aspect of metabolic control. This is accomplished with the aid of the ubiquitin system (Box 10-C) and proteasomes (Box 7-A).107 Proteins secreted into extracellular fluids often undergo more rapid turnover than do those that remain within cells. 

Deamidation, isomerization and racemization. These three reactions are common degradation pathways of proteins and peptides. These reactions are especially prevalent for peptides containing asparagine (Asn) and glutamine (Gin) residues. In the deamidation reaction, the Asn or Gin amide... 

Figure 5-2. Chemistry of the Edman degradation. In the Edman degradation, peptides undergo reaction with phenylisothiocyanate which generates a phenylthiocarbamylpeptide adduct. This adduct is cleaved to release the...

S complexes can form which function in specific degradation reactions. In the pro-teasome that is involved in processing antigenic peptides the catalytic reactions are performed by E-subunits different from the the X,Y and Z subunits. This specific proteasome is also called immunoproteasome . 

Secondly, the substrate concentration of the reaction medium is an important factor in peptide bond resynthesis and, as seen from Figure 1, should be in the range of 20-40% (w/v). When a substrate is incubated at a concentration of about 7.5% (Figure 1), no reaction appears to occur as measured by trichloroacetic acid-solubility/insolubility. Lower substrate concentrations are more favorable for the degradation reaction. 

Not only transpeptidation, but also a certain amount of peptide-peptide condensation, is possibly involved in the plastein reaction. With some of the proteases used for plastein formation, especially a-chymotrypsin (26, 52, 53, 54), the acyl-enzyme intermediate can be formed at pHs 5 from the reversal of the degradative reaction (Equation 1 E-OH + HOOC-CHR-NH E-O-OCCHR-NH- + H20). Once the acyl-enzyme intermediate is formed, the acyl group can be transferred to a nucleophile resulting in peptide bond synthesis. 

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