Other peptides

Other peptides occur commonly and in variable levels in protein rich food as degradation products of proteolytic processes. 

Like peptides, proteins are formed from amino acids through amide linkages. Covalently bound 

The structure of a protein is dependent on the amino acid sequence (the primary structure) 

From sponges of the genus Jaspis collected at Fiji (300,301), Palau (300), and Papua New Guinea (302), jaspamide (jasplakinolide, 372) was isolated the compound shows potent insecticidal, antifungal, anthelminthic, and ichthyotoxic activity. The structure was determined by X-ray analysis (300). The solution conformation of372 was reported using NMR, molecular mechanics, and dynamics calculations (303). A complexation study was carried out with 372 and the univalent metal ions Li , Na+, and K+. Li+ binding was observed, and the complex was characterized by NMR and molecular mechanics calculations (304). Jaspamide (372) has potent in 

Four antimicrobial peptides, discodermins A-D (383-386), isolated from the Japanese sponge Discodermia kiiensis also show inhibitory activity on the development of starfish embryos (317,318). Three ichthyo-toxic peptides, pardaxins P-1 through P-3 (387-389), were isolated from 

A Caribbean cyanobacterium Hormothamnion enteromorphoides was found to produce a complex mixture of cytotoxic and ichthyotoxic peptides, hormothamnins, which may explain the apparent absence of predation on these potentially palatable life forms. Initial chemical characterization suggested that the major peptide, hormothamnin A, is a cyclic undecapeptide containing six common and five uncommon amino acid residues (320). 

Detection Nonactin by spraying with cone. H2SO4 and heating to 150° C, or with the Dragendorff reagent. Microbiological detection of nonactin with Staph, aureas. ATTCC6538P cyanein with Candida pseudotropicalis rifomycins with Sarcina lutea ATCC 9341 novobiocin with Bac. subtilis ATCC 6633 chloramphenicol with Sarcina lutea ATCC 9341. 

The air-dried material was extracted 3 times in water over a boiling water bath for about 30 min. The resulting extract was poured off and the residual plant material freed from adherent liquid in a press. The combined extracts were then precipitated with basic lead acetate and filtered. The filtrate, after removal of Pb by HjS04, was treated with Ba(OH)j to remove SO, and was concentrated under reduced pressure. The solution was then precipitated by mercuric acetate, and the resulting Hg salt, after washing, was decomposed with HjS, filtered from HgS, and evaporated to dryness in a vacuum. 

The amount of crude peptide occurring in the algae varies from 0.05 to 0.29% of the dry weight. In Pelvetia, however, the amount is as high as 0.73%. 

The qualitative composition in amino acids of these peptides is given in Table XIII. Haas (238) suggested that these peptides may be intermediate products of protein metabolism resulting from deficient synthetic activity caused by unfavorable conditions of growth, either as regards illumination or moisture. 

On the other hand, a peptidelike substance, eisenin, was isolated by Ohira (440,441,442) from Eisenia bicyclis, using, a similar procedure to that of Haas. On hydrolysis it yielded L-alanine L-glutamic acid, and ammonia. Ohira formulated eisenin as pyrrolidonoylglutaminylalanine. This conclusion has been criticized by Tazawa (582). 

Quantitative Composition of Peptides from Several Algae (238,242) 

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A major advance was devised by Pehr Edman (University of Lund Sweden) that has become the standard method for N terminal residue analysis The Edman degrada tion IS based on the chemistry shown m Figure 27 12 A peptide reacts with phenyl iso thiocyanate to give a phenylthwcarbamoyl (PTC) denvative as shown m the first step This PTC derivative is then treated with an acid m an anhydrous medium (Edman used mtromethane saturated with hydrogen chloride) to cleave the amide bond between the N terminal ammo acid and the remainder of the peptide No other peptide bonds are cleaved m this step as amide bond hydrolysis requires water When the PTC derivative IS treated with acid m an anhydrous medium the sulfur atom of the C=S unit acts as... 

CGRP has a wide distribution in the nervous system (19) and was the first peptide to be localized to motoneurons (124). It is also found in primary sensory neurons where it is colocalized with substance P (125). CGRP is derived from a precursor stmcturaHy related to the calcitonin precursor. The latter precursor produces two products, calcitonin itself and katacalcin, while the CGRP precursor produces one copy of CGRP (123). Like other peptides, CGRP is cleaved from its precursor by tryptic breakdown between double basic amino acid residues. 

FIGURE 5.19 N-Tertninal analysis using Edman s reagent, phenylisothiocyanate. Phenylisothiocyanate combines with the N-terminus of a peptide under mildly alkaline conditions to form a phenylthiocarbamoyl substitution. Upon treatment with TFA (trifluo-roacetic acid), this cyclizes to release the N-terminal amino acid residue as a thiazolinone derivative, but the other peptide bonds are not hydrolyzed. Organic extraction and treatment with aqueous acid yield the N-terminal amino acid as a phenylthiohydantoin (PTH) derivative. 

Complex II is perhaps better known by its other name—succinate dehydrogenase, the only TCA cycle enzyme that is an integral membrane protein in the inner mitochondrial membrane. This enzyme has a mass of approximately 100 to 140 kD and is composed of four subunits two Fe-S proteins of masses 70 kD and 27 kD, and two other peptides of masses 15 kD and 13 kD. Also known as flavoprotein 2 (FP2), it contains an FAD covalently bound to a histidine residue (see Figure 20.15), and three Fe-S centers a 4Fe-4S cluster, a 3Fe-4S cluster, and a 2Fe-2S cluster. When succinate is converted to fumarate in the TCA cycle, concomitant reduction of bound FAD to FADHg occurs in succinate dehydrogenase. This FADHg transfers its electrons immediately to Fe-S centers, which pass them on to UQ. Electron flow from succinate to UQ,... 

Alternate ways to interfere with the orexin system may be via inhibition of dipeptidyl peptidases or proteolysis-resistant peptide analogs as shown for other peptides. This could prolong and boost orexinergic signaling. OX-A but not OX-B can enters the brain by simple diffusion via the blood-brain barrier. Abundance of orexins and their receptors in the olfactory bulb and throughout all parts of the central olfactory system may offer transnasal routes for drug application. 

ACE not only activates angiotensin but is also involved in the metabolism of other peptides, e.g., it is a major kinin-degrading enzyme. Therefore, ACE inhibitors also increase kinin concentrations. Furthermore, it has recently been shown that these drugs potentiate kinin effects by modulating a direct interaction between the ACE protein and the kinin B2 receptor, which is independent from the enzymatic activity of ACE. Kinin potentiation may be involved in the beneficial action of ACE inhibition since kinins are known to exert cardio- and renoprotective actions. 

Except substance P (SP), the first mammalian tachykinin (TK) peptide to be sequenced (by Chang and Leeman in 1970), other peptides belonging to TK family have synonyms. This is due to historical reasons,... 

Other peptides that have been linked to the actions of ethanol are corticotropin-releasing factor, urocortin, leptin, cholecystokinin, melanocortins, and galanin (for reviews, see Cowen et al. 2004 Egli 2003 Thiele et al. 2003). 

In mammals, peptide hormones typically contain only the a-amino acids of proteins finked by standard peptide bonds. Other peptides may, however, contain nonprotein amino acids, derivatives of the protein amino acids, or amino acids finked by an atypical peptide bond. For example, the amino terminal glutamate of glutathione, which participates in protein folding and in the metabolism of xenobiotics (Chapter 53), is finked to cysteine by a non-a peptide bond (Figure 3—3). The amino terminal glutamate of thyrotropin-... 

Many other peptides are synthesized as proproteins that require modifications before attaining biologic activity. Many of the posttranslational modifications involve the removal of amino terminal amino acid residues by specific aminopeptidases. Collagen, an abundant protein in the extracellular spaces of higher eukaryotes, is synthesized as procollagen. Three procol-... 

The a -, /z-, and a-conotoxins are the best characterized of the peptides isolated from Conus venoms so far. However, a large number of other peptides are found in these venoms. These comprise both paralytic toxins to immobilize the prey of the cone snail, and other biologically active peptides which are not themselves directly paralytic. Only the briefest overview of these peptide components will be presented here. 

The peptides will now be considered individually in some detail. It must be noted that the large molecular size of the peptides means that they are even less likely to cross the blood-brain barrier than classical transmitters and the instability of peptides means that full functional studies require non-peptide agonists and antagonists. Whereas nature has provided morphine and medicinal chemists have made naloxone, tools are lacking for many other peptides. 

A number of other peptide molecules are currently being explored for delivery via inhalation (6). Very recently, a much smaller peptide (leuprolide, about 9 amino acid residues) has been delivered by metered dose inhaler (MDI) in a characterized fashion to humans (7). This work revealed that about 50% of a dose deposited in the lung could be bioavailable. This value is much greater than those reported for nasal bioavailabilities of this and similar molecules (8). These results, and ours in the rat lung (9), imply that inhalation administration of some peptide and polypeptide molecules is perfectly feasible. 

Calcitonin and other peptide products of the calcitonin gene are known to be el-... 

As is the case with identifications based on protein molecular masses, it appears that the use of tryptic or other peptide masses as the basis for identification is extended with difficulty to mixtures of microorganisms. This reflects unpredictable suppression. Another limitation is redundancy of peptide masses across several microorganisms. For example, the most abundant proteins (SASPs), and thus the most abundant peptides, in spores of Bacillus anthracis and the closely related pesticide Bacillus thuringiensis have extensive sequence homology.25,82... 

The vast majority of neuropeptides that have been structurally characterized from nematodes are FaRPs. One other peptide, TKQELE,... 

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