C-terminal amino acid residue

Although removal of Trp from unmodified ACTH-(4-9) or removal of Met from ACTH-(4-10) resulted in no and some loss of activity, respectively, leaving out the N- or C-terminal amino acid residue in [Met(02), D-Lys , Phe ]ACTH-(4-9) resulted in a considerable loss of activity (by a factor of 1000 and 30-100, respectively). So for potentiation the presence of the side-chains of Met(02), D-Lys and Phe seems to be of prime importance. 

The C-terminal amino acid residue of a segment, which is to be coupled with the amino group of another segment, should be selected from group A or B in Table 1, but not from group C. 

Table 1 C-Terminal Amino Acid Residues Acceptable for Segment Condensation Reactions...

Great care has to be taken in the analytical characterization of synthetic cyclic peptides.[73] The major side reactions during cyclization are epimerization of the C-terminal amino acid residue and cyclodimerization. Cyclodimers can be detected by mass spectrometry, although the analysis is not trivial, because artifacts do occur in some ionization techniques such as ES-MS as a result of aggregation.1 1 Ll 121 Real dimers can be detected as double-charged particles with mlz values identical to the cyclic monomers, but with a mass difference of 0.5 amu in the resolved isotope signals. The mass difference of the corresponding monomer is 1 amu. The cyclodimerization has received some attention as a direct method for the synthesis of C2-symmetrical cyclic peptides.[62 67 94113 115]... 

Carboxypeptidase A"" (CPA, EC 3.4.17.1) is a proteolytic enzyme that cleaves C-terminal amino acid residues with hydrophobic side chains selectively. Several X-ray structures are available" The active site of CPA consists of a hydrophobic pocket (primary substrate recognition site) that is primarily responsible for the substrate specificity, a guanidinium moiety of Argl45 that forms hydrogen bonds to the carboxylate of the substrate, and Glu270, whose carboxylate plays a critical role, functioning either as a nucleophile to attack the scissUe carboxamide carbonyl carbon of the substrate or as a base to activate the zinc-bound water molecule, which in turn attacks the scissile peptide bond ". However, semiempirical calculations had shown that the direct attack of... 

The carboxypeptidases are released from their inactive precursors in the pancreatic juice of animals. The most studied example is bovine carboxypeptidase A, which contains one mole of zinc per protein molecular weight of 34 500. These enzymes cleave the C-terminal amino acid residue from peptides and proteins, when the side-chain of the C-terminal residue is aromatic or branched aliphatic of l configuration. At least the first five residues in the substrate affect the activity of the enzyme. The enzyme also shows esterase activity. Esters and peptides inhibit each other competitively, indicating that the peptidase and esterase sites overlap, even if they are not the same. 

To localize ER[3 in frozen sections, antigen retrieval with heating is not required. 210-180-C050 antibodies (Alexis Corporation, Nottingham, UK) are obtained by immunizing rabbits with synthetic peptides representing the C-terminal amino acid residues 467-485 of human estrogen. 

The rate of hydrolysis of benzyoxycarbonyl-L-Glu-L-Tyr (Z-Glu-Tyr) is arbitrarily taken to be 100. C-terminal amino acid residues of the substrates are expressed as R-X-Y. 

Figure 16.13 Structures of glucagon and the digestive hormones, indicating their homologies. (Asterisk indicates amidation of C-terminal amino acid residue, which occurs with some gut hormones.) (Reproduced by permission from Tietz NW, Rinker AD, Henderson AT. Gastric, pancreatic, and intestinal function. In Tietz NW, ed. Textbook of Clinical Chemistry. Philadelphia WB Saunders, 1986, p. 1439.)...

Fig. 8-4 The mechanism of covalent catalysis of the hydrolysis of a C-terminal amino acid residue from a peptide by carboxypeptidase A. The reaction is (a) —> (d), and the bold line structure is the peptide substrate. The C-terminal tyrosine side chain of the substrate shown in (a) is denoted by in (ft), (c), and (d).

In 1996, Tamura and Stadtman showed that thioredoxin reductase from mammalia-in contrast to the bacterial homologs-is a selenoprotein, and that selenocysteine is the penultimate C-terminal amino acid residue. Selenium-containing isoenzymes, which are tissue specific, have later on been characterized biochemically, or the existence of such isoforms was suggested by in-sihco methods. The substrate of thioredoxin reductase is thioredoxin, which is the key regulator of the redox status within cells. Thioredoxin catalyzes thiol-disulfide exchange reactions in proteins and peptides it is involved as redox mediator in the... 

The principles of SPPS are illustrated in Fig. 2. The A -protected C-terminal amino acid residue is anchored via its carboxyl group to a hydroxyl (or chloro)... 

A convenient way of representing peptide structures by use of standard abbreviations (see Table 36.1) is illustrated here. According to convention, the N-terminal amino acid residue (having the free amino group) is written at the left end, and the C-terminal amino acid residue (having the free carboxyl group) at the right end. 

In their physiological functions, proteins are highly specific. We have encountered, for example, an enzyme that will cleave a-glucosides but not ) -gluco-sides, and an enzyme that will cleave only C-terminal amino acid residues in polypeptides. It seems clear that the biological activity of a protein depends not only upon its prosthetic group (if any) and its particular amino acid sequence, but also upon its molecular shape. As Emil Fischer said in 1894 . . enzyme and... 

C-terminal amino acid residue See amino acid... 

C-terminal racemisation of a peptide and specific deuteration of the C-terminal residue can be achieved by cyclisation of the peptide to the peptide oxazolone and quenching in 2H20. This specific reactivity of the C-terminal amino-acid residue has formed the basis of a C-terminal analysis of peptides the C-terminal residue is the only one to be racemised in this way and the identity of the C-terminal residue is revealed by analytical methods for determining d l ratios of amino-acid mixtures (Section 4.18.2 Sih and Gu, 1995). 

Mild oxidation of the C-terminus of a peptide can bring about the formation of an acylimide, which is then easily hydrolysed. This change, which is thought to involve oxidative a-hydroxylation of the C-terminal amino acid residue (or oxidation of the oxazolone formed from the C-terminal amino acid residue) has been accomplished under physiological conditions in the absence of enzymes when the C-terminus is activated as an anhydride or as an oxazolone (the reactions are shown in Scheme 8.3 Barrett et al., 1978) and the search for an enzymic equivalent has led to the discovery of a family of amidating enzymes. This, then, is how a biologically inactive propeptide , with one amino-acid residue more than the peptide amide into which it is processed, is a latent precursor for many hormones that are peptide amides (calcitonin, vasopressin, etc.). 

The difference between this mass value and the mass value of the next lower peak (C), represents the mass of the esterifying group OR. The difference between the mass value of (C) and that of the next lower mass peak (D), represents the mass of CO (28 atomic mass units). The difference between the mass value of (C) and that of (E) represents the mass of the C-terminal amino acid residue of the original peptide, whereas the difference between (D) and (E) is the mass of the imine HN=CHR. 

Cl. Cahill, C. L., and Li, S. C., Terminal amino acid residues of ovine follicle stimulaV ing hormone. Biochim. Biophys. Acta 168, 367-369 (1968). 

Determination of C-terminal amino acid residues by use of hydrazine. 

In contrast to the cellular environment, where enzymatic degradation of proteins is highly controlled, extracellular proteases are the cause of uncontrolled protein degradation. The result of this proteolytic attack may vary from complete hydrolysis, single breaks within the peptide chain, or loss of a few N- or C-terminal amino acid residues. Besides losing the product, presence of truncated forms may seriously challenge the purification design. 

The C-terminal amino acid residues preferred by TAP match with those generated by the proteolytic activities of the proteasome [23], as well as with C-terminal anchors used by most human class I molecules (database S YFPEITHI www.medizin.uni-tuebingen.de/ sfb510/index.html) [24]. 

Met-enkephalin and leu-enkephalin belong to a group of peptides called the opioid peptides, found predominantly in nerve tissue cells. Opioid peptides are molecules that relieve pain (a protective mechanism in animals that warns of tissue damage) and produce pleasant sensations. They were discovered after researchers suspected that the physiological effects of opiate drugs such as morphine resulted from their binding to nerve cell receptors for endogenous molecules. Leu-enkephalin and met-enkephalin are pentapeptides that differ only in their C-terminal amino acid residues. Substance P and bradykinin stimulate the perception of pain, an effect opposed by the opioid peptides. 

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