Basics of Biochemistry - Filippovich, Y. B. 1999

Proteins
Peptides

One of the important Chemical properties of α-Amino Acids, arising from the simultaneous presence of amino and carboxyl groups in the molecule, is their ability to form Peptides under certain conditions. The scheme of this process, which proceeds via a polycondensation reaction type, is as follows:

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In reality, the process in the living Organism is much more complex. This reaction will be examined in detail when studying Protein METABOLISM. The aforementioned peptide formation reaction from amino acids is of great importance for understanding the Chemical Structure of protein bodies.

As a result of the polycondensation of amino acids, compounds consisting of numerous amino acid residues with very high molecular weights can be obtained. Such compounds are called Polypeptides, and the —CO—NH– groups within them are referred to as peptide groups or peptide bonds. Peptides can also be obtained through the incomplete Hydrolysis of Proteins.

Since amino acids within peptides are in the acyl form, the acyl-characteristic suffix "-yl" is added to their name in the peptide nomenclature. The name of the C-terminal amino acid with a free carboxyl group is left unchanged. The naming of a peptide begins with The amino acid that has retained its free α-amino group.

Nowadays, the term "peptides" has lost its original meaning, since peptides were once understood to be the End products of Protein Digestion, i.e., essentially α-amino acids. Therefore, it was logical to call digestion products composed of two amino acid residues (peptides) dipeptides, and those composed of many residues, polypeptides. It is much more accurate to refer to peptides as heteropolyamino acids, i.e., compounds composed of a certain number of various amino acids. However, the term peptides has firmly established itself in Protein Chemistry, albeit with a new meaning.

Fig. 21. Scheme of solid-phase Peptide and Protein synthesis

In laboratory settings, peptides can be obtained through various Methods, the common feature of which is the mandatory Protection of the amino group in one reacting Amino Acid and the carboxyl group in the other, so that they can participate in the Condensation reaction exclusively via the remaining free (or chemically activated) carboxyl (COOH-) or amino (NH₂-) group. The solid-phase Peptide Synthesis method, proposed by R. Merrifield, has gained the greatest prominence (Fig. 21). Here, the COOH- group of the starting amino acid is protected by attachment to a polymer, while the NH₂- group of the incoming amino acid is protected by a tert-butyloxycarbonyl (Boc) radical. This method is amenable to automation, and an automated synthesizer has been developed on its basis, which is used to synthesize not only peptides but also proteins.

Several hundred individual peptides have been isolated from natural sources, and in many cases, their structure, properties, and biological activity have been studied in detail. Let us consider a few Examples.

Glutathione (γ-glutamylcysteinylglycine, γ-glu-cys-gly) is one of the most widespread intracellular peptides, taking part in cellular redox processes and the Transport of Amino acids across Introduction/36.html">Biological Membranes:

Glutathione was discovered by F. Hopkins in 1921. It is a crystalline powder with a melting point (t_pl) of 190–192°C. From a solution in 0.5 N H₂SO₄, it precipitates

as an insoluble copper mercaptide upon The addition of Cu₂O.

The formula given above corresponds to the so-called reduced glutathione (HS-glutathione). Along with the reduced form of glutathione, the oxidized form (SS-glutathione) is always present in The Cell and is converted back to the reduced form through the mediation of the enzyme glutathione reductase:

Ophthalmic acid (γ-glutamyl-α-aminobutyrylglycine) is a glutathione antagonist, just as widely distributed in nature as glutathione itself:

Present in Cells in trace amounts ranging from 0.1 to 0.001 of the glutathione concentration, ophthalmic acid acts as an inhibitor in processes involving glutathione.

Carnosine (β-alanylhistidine; β-ala-his) is a peptide found in animal Muscle tissue:

It prevents the accumulation of and scavenges Lipid Peroxidation products, helps maintain the buffer capacity of muscle fluid, accelerates carbohydrate breakdown in Muscles, and, in the form of phosphate, is involved in muscle Energy Metabolism. Carnosine was first isolated from muscle tissue and its structure elucidated by V. S. Gulevich.

The Role of peptides in vital processes is extremely diverse. Many of them serve as Hormones (see Chapter XII), some are potent toxins (venoms of snakes, toads, snails, spiders, insects, higher Fungi, and microbes), powerful Antibiotics, releasing factors (promoting hormone synthesis and release), regulators of Cell Division, carriers of molecules and ions across biological membranes, and regulators of mental activity. A significant number of Natural peptides have been synthesized; moreover, hundreds of their analogs have been artificially produced, some of which exhibit stronger biological activity than their natural precursors. Both find widespread Practical Application. The structure of some of these is shown in Fig. 22.