Peptides of animal origin

Camosine was first isolated from beef extract by Gulevitsch and Amiratzibi (236,237) in 1900. After the work of Gulevitsch (235), its structure was established by Baumann and Ingvaldsen (49) and by Barger and Tutin (35) who eventually synthesized it. 

One starts with an aqueous meat extract, acidifies with acetic acid, then adds phosphotungstic acid, to form a precipitate. This precipitate is treated with baryta, the mixture filtered, and the filtrate is neutralized with nitric acid. Silver nitrate is added, and the precipitate which forms is eliminated. The carnosine is precipitated from lie filtrate by the addition of silver nitrate in the presence of baryta. The precipi- 

A better procedure, giving a 65% yield, was worked out later by Sif-ferd and du Vigneaud (526). Carbobenzoxy-j8-alanine is converted to the azide which is condensed with the methyl ester of histidine. This method has been somewhat improved by Hanson and Smith (256). 

After extraction of carnosine, one can determine the peptide concentration by a complete hydrolysis, followed by an assay for histidine, either enzymatically (decarboxylase) or microbiologically (291,631). 

Carnosine is also present in the muscles of lower vertebrates such as frog (165) or fish (330), but it is not present in mammalian brain (165) nor in invertebrate muscle (131,165). 

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The methods employed to deduce the structures of peptides have been reviewed by several authors and are not commented on here. These methods, when applied to peptides of animal origin with their limited number of amino acids, can be used with a minimum amount of peptide and the released amino acids or their reaction products can usually be identified unequivocally by chromatographic procedures. In the case of peptide antibiotics with their many uncommon constituents, the characterization of these components is an additional task. Even the amino acids themselves need a careful investigation. They may be derivatives of common amino acids, they may be secondary degradation products from unusual components, or they may have D-configuration. Therefore the components have usually to be isolated in amounts which allow a careful chemical and physicochemical characterization, and often direct comparison with synthetic compounds is necessary. 

A number of peptides of animal origin were shown to play a role in cancer therapy as antimetabolites. Later, several peptide antibiotics were demonstrated to have similar properties. One of these, cyclosporin A (5), produced by certain fungi imperfecti, was shown to prevent attack on host tissues by transplanted cells (Sneader, 1985). Another series of peptides from Streptomyces verticillus, of which bleomycin A2 (Fig. 14.2) is the main component used clinically, has pronounced antitumor activity. The most striking feature... 

Table 5.1 Some biologically active peptides of animal origin...

L. Jacob, M. Zasloff (1994). Potential therapeutic applications of magninins and other anti-microbial agents of animal origin. In J. Marsh, J.A. Goods, (Eds), Antimicrobial peptides (Vol. 186, pp. 197-223). Ciba Foundation Symposium, John Wiley and Sons, Chichester, UK,... 

A09A A Enzyme Preparations Enzymes can be used therapeutically. Some are of animal origin (from the stomach and pancreas of food animals), some of vegetable origin and others of microbiological origin. Examples of the first type include pepsin and pancreatin, a mixture of amylase, lipase and trypsin (a protease) which catalyses the metabolism of proteins into smaller peptides and amino-acids. Pancreatin is frequently prescribed for patients with cystic fibrosis. 

Alkaloids - Basic nitrogen compounds (mostly heterocyclic) occurring mostly in the plant kingdom (but not excluding those of animal origin). Amino acids, peptides, proteins, nucleotides, nucleic acids, and amino sugars are not normally regarded as alkaloids. [5]... 

In plants that strongly accumulate selenium, this element is present mainly in the form of free selenium amino acids and peptides. Selenimn in foods is mainly in the form of selenium amino acids bound in protein molecules. In most plant foods, the major form of selenium is selenomethionine. For example, total selenium concentrations for Canadian lentils ranged from 0.16 to 0.72 mg/kg and almost all the selenium (86 95%) is present as selenomethionine with a small part (5 14%) as selenate, but the main components ofgarKc are selenocysteine and organic selenides. In foods of animal origin, the majority of selenium is bound in selenocysteine. 

Bloom et al. (75,76) described a basic peptide of leucocyte origin, pancreas, and normal thymus (see p. 103). This peptide, containing a significant amount of lysine, has the property of blocking the respiration of B. anthracis and other bacterial species, and is therefore capable of protecting animals against infection by B. anthracis. It is of singular interest that these activities of the basic peptide are inhibited by the inflammatory factor as well as by DGP of B. anthracis. 

A number of insects and higher animals have also been found to possess unusual small organosulfur molecules which may serve as defensive secretions, sex attractants, or scent markers. In many cases the low molecular weight organosulfur compounds occur in plants (and possibly in animals as well) in an odorless combined form (e.g., as peptides or glycosides) and are released enzymatically when the tissue is injured or stimulated, i.e. during attack by a predator. Finally it should be noted that certain sulfur compounds reported to be of natural origin may... 

Systematic substitutive nomenclature may be used to name all organic molecules. However, those that are of animal or vegetable origin have often received trivial names, such as cholesterol, oxytocin and glucose. Biochemical nomenclature is based upon such trivial names, which are either substitutively modified in accordance with the principles, rules and conventions described in Chapter 4, Section 4.5 (p. 70), or transformed and simplified into names of stereoparent hydrides, i.e. parent hydrides of a specific stereochemistry. These names are then modified by the rules of substitutive nomenclature. Three classes of compound will be discussed here to illustrate the basic approach carbohydrates amino acids and peptides and lipids. For details, see Biochemical Nomenclature and Related Documents, 2nd Edition, Portland Press, London (1992). 

Further aliphatic a-methyl-/ -amino acids, for example Amha 69, Admpa 70, and Amoa 73, have been found in peptidic natural products from marine animals and from cyanobacteria. Although dolastatin D 82 and dolastatin 17 83 have so far been obtained from sea hare isolates only, these peptides should now be considered to be of cyanobacterial origin, as indicated by their p-amino acid substructures, i.e. Amba 67 and Aoya 72. 

The contributions of Richard Block to the serum protein problem originated from the hypothesis of Kossel. From recent data on the amino acid composition of the proteins found in animal sera, a formulation is derived which reflects the properties of a continuous system of molecular species originating from a common biosynthetic pathway, as if from mixed polymers of monomeric peptides of lower molecular weight. Indirect evidence of this is found in the amino acid interrelationship, and direct evidence is limited to the isolation of peptides of common composition, whose primary structures are still under investigation. These findings suggest that undifferentiated proteins may be continuous systems rather than discrete molecular species. 

In most connective tissues of animals, the acidic mucopolysaccharides are complexed with protein or peptide residues. Little is known about the structure of these complexes, and the term mucopolysaccharide is therefore best applied only to the pure polysaccharide. When the latter is complexed with protein, it has been suggested (J5) that a noncommittal term such as hyaluronic acid-protein complex should be used. Many of the names originally assigned to the acidic mucopolysaccharides have since been revised (J5) in an effort to systematize the nomenclature. The more systematic names proposed by Jeanloz (J5) will generally be used throughout this review, but whenever possible synonymic names have been given. 

This classification does not apply to biological/biotechnological, peptide, oligonucleotide, radiopharmaceutical, fermentation and semisynthetic products derived therefrom, herbal products, and crude products of animal or plant origin. 

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