Structural Biochemistry - Study Guide - E. A. Bessolitsyna 2015

When the carboxyl group of one α-amino acid acylates the amino group of another, the resulting amide bond is referred to as a peptide bond, and the compound itself as a peptide. Thus, Peptides are compounds constructed from α-amino acid residues linked together by peptide bonds. For relatively long peptides, the term Polypeptides is sometimes used. It is worth noting that other amide bonds can also form involving Amino Acids—for instance, between the γ-carboxyl group of a glutamic acid residue and the ε-amino group of Lysine during fibrin chain cross-linking as a thrombus ages. Although chemically similar to peptide bonds, such linkages are not classified as such and are sometimes called isopeptidic bonds. The formation of peptide bonds in Water is thermodynamically unfavorable, which necessitates the preliminary activation of the interacting groups (most commonly the carboxyl group) during both the chemical synthesis and The Biosynthesis of a peptide. Nevertheless, kinetically the peptide bond is quite stable, and its hydrolytic Cleavage occurs only through The Use of chemical catalysts (acids or bases) or via catalysis by specific Enzymes (peptidases). Naturally, a dipeptide formed by the Condensation of two amino acid residues retains both the carboxyl and the amino groups; therefore, The addition of further amino acid residues can continue from both ends, making it possible to form very long peptide chains consisting of hundreds or even thousands of amino acid residues. A peptide chain features an N-terminal (or amino-terminal) residue containing a free amino group, and a C-terminal residue bearing a free α-carboxyl group.

The Physical Properties of peptides depend on their constituent amino acids. If a peptide contains phenylalanine, Tyrosine, and Tryptophan, it will absorb UV radiation, with an absorption maximum at a wavelength of 280 nm. Their water solubility varies and is determined by both the peptide's length and The Nature of its constituent amino acids. The higher the proportion of hydrophobic amino acids in a peptide, the lower its solubility in water.

Like amino acids, peptides containing free amino and carboxyl groups exist as zwitterions and possess an isoelectric point. However, when determining the isoelectric point, the side-chain Functional groups of The amino acid residues exert a greater influence. The acid-base properties of peptides differ somewhat from those of amino acids, since the mutual Influence of the amino and carboxyl groups is significantly weaker than in α-amino acids, and in long peptides it can be neglected entirely. In peptides, the pK_a of the α-carboxyl group is noticeably higher than in amino acids; for example, it is 3.12 for alanyl-Alanine (cf. a pK_a of 2.34 for the carboxyl group of alanine and 4.7 for acetic acid). For the carboxyl group of alanyl-alanyl-alanine, the pK_a is 3.39, and with further chain elongation, the value remains close to 3.4.

A slight increase in acidity compared to the carboxyl group of acetic acid should be attributed to METABOLISM/18.html">The Influence of the adjacent peptide bond. Similarly, the alpha-amino group in peptides is less basic than in α-amino acids: the pK_a of the α-ammonium group is 9.69 for alanine, 8.30 for alanyl-alanine, and 8.03 for alanyl-alanyl-alanine, remaining unchanged with further chain lengthening.

In all other respects, The chemical properties of the α-amino and carboxyl groups of peptides are qualitatively similar to those of amino acids. In particular, they undergo the same reactions described for amino acids, except for those involving the simultaneous participation of both functional groups, which are not characteristic of peptides. An exception is the relatively facile cyclization of esters and certain other dipeptide derivatives with an activated carboxyl group, leading to diketopiperazines. In strongly alkaline solutions, peptides yield complex colored complexes with copper ions, which is The basis of the so-called biuret test. Naturally, peptides can also participate in reactions driven by the functional groups located in the amino acid side chains.

In Prokaryotic Cells, peptides are synthesized by specialized transpeptidases in a non-ribosomal manner. In eukaryotes, the Peptide Structure is encoded in The Genome as a larger precursor polypeptide protein. Transcription occurs first, followed by Protein Biosynthesis on an mRNA template by the ribosome to produce a precursor protein, which subsequently undergoes Limited proteolysis by specific enzymes that target strictly defined bonds to release active peptides.

Peptides act as intermediates in protein degradation.

Peptide Antibiotics are largely synthesized by microorganisms via a specialized non-ribosomal mechanism and contain A number of non-protein Amino acids as well as D-isomers. Many of these are cyclic peptides. Notable among such antibiotics is the cyclodecapeptide gramicidin S, a broad-spectrum antimicrobial agent. Attention should be drawn to the presence of the non-protein amino acid Ornithine and the D-isomer of phenylalanine in its molecule.

Another effective immunosuppressive cyclic peptide antibiotic is cyclosporine, which contains N-methylated and other non-protein amino acids (an unsaturated hydroxy amino acid, aminobutyric acid, and a D-alanine residue). Recently, peptide antibiotics produced by animal cells, particularly lymphocytes, have been discovered; these are formed via the conventional pathway of protein biosynthesis.

Peptide Hormones—and more broadly, regulatory peptides—play a critical role in controlling metabolic processes, organismal development, and signal Transduction. These include several short peptides, such as oxytocin, which stimulates uterine contractions and Lactation. The nonapeptide vasopressin has a similar structure and acts to suppress diuresis while elevating Blood pressure. Adrenocorticotropic hormone (ACTH), whose peptide chain consists of 39 amino acid residues, regulates Adrenal gland function and can influence a wide range of processes, including motivation, learning, and behavior. Melanocyte-stimulating hormone controls melanin production in vertebrate pigment cells, but also affects Nervous system function, behavioral responses, and fetal development. It should be noted that the functions of peptide hormones are generally multifaceted, and it is often possible to isolate distinct sequence regions responsible for specific types of biological activity. Post-translational modifications are characteristic of peptide hormones: in the case of α-melanocyte-stimulating hormone, these include Acetylation of the α-NH₂ group and amidation of the α-carboxyl group.

Enkephalins are peptides that interact with the same receptors as morphine and function as natural analgesics. They are synthesized as precursors in whose peptide chain the enkephalin sequences Tyr — Gly — Gly — Phe — Leu or Tyr — Gly — Gly — Phe — Met are repeated multiple times. These sequences are preceded and followed by Arg — Arg pairs, which serve as a signal for a specific proteinase that cleaves the peptide bond following such an Arginine pair. Both arginine residues are subsequently removed by a specific carboxypeptidase, releasing the free enkephalin. Often, peptides can mimic The behavior of corresponding protein fragments in their interactions with other biological molecules—specifically other Proteins, such as receptors or structural molecules. For instance, the pentapeptide fragment of the Connective Tissue protein Laminin, with the sequence Tyr — Ile — Gly — Ser — Arg, is responsible for Cell Adhesion to this protein. A pentapeptide of identical structure is capable of inhibiting this process, presumably by blocking cell-surface receptors involved in laminin binding.

Immune-regulatory peptides. These include Thymus hormones and the tetrapeptide tuftsin (Thr — Lys — Pro — Arg), which is a fragment of the CH2 domain of immunoglobulin G.

Among peptides, there are substances exhibiting high toxicity—such as toxins from bee and wasp venom, peptides from the death cap mushroom (phalloidin, amanitins, etc.), snake venom neurotoxins, botulinum toxin (which blocks neuromuscular transmission of nerve impulses), and diphtheria toxin (which inhibits protein biosynthesis).

Biologically active peptides include anserine, Glutathione, and carnosine, which participate in biochemical reactions within animal Tissues. The BIOLOGICAL FUNCTIONS OF glutathione include: protecting the SH groups of enzymes and other proteins from oxidation; reducing H₂O₂ and other peroxides; scavenging free radicals; participating in thiol-disulfide exchange and the Detoxification of Various xenobiotics; reducing ribonucleotides to deoxyribonucleotides; transporting amino acids across cell membranes; and acting as a cofactor for a number of enzymes, such as glyoxalase and formaldehyde dehydrogenase.

Peptide Alkaloids contain a peptide residue in their molecule, usually cyclic (hence they are often referred to as cyclopeptide alkaloids). This category also includes alkaloids containing a hydroxystyrylamine fragment. Peptide alkaloids are most prevalent in plants of the buckthorn family (Rhamnaceae). They are found in the leaves, bark, roots, and other plant parts in amounts ranging from 0.02 to 1%. Certain plant species containing peptide alkaloids are used in traditional medicine to treat diarrhea and dysentery. A number of peptide alkaloids exhibit activity against lower Fungi and Bacteria.