Peptide carboxyl terminal

To illustrate the specific operations involved, the scheme below shows the first steps and the final detachment reaction of a peptide synthesis starting from the carboxyl terminal. N-Boc-glycine is attached to chloromethylated styrene-divinylbenzene copolymer resin. This polymer swells in organic solvents but is completely insoluble. ) Treatment with HCl in acetic acid removes the fert-butoxycarbonyl (Boc) group as isobutene and carbon dioxide. The resulting amine hydrochloride is neutralized with triethylamine in DMF. 

Evidence soon emerged that the endogenous opioids were peptides rather than simple morphine-like molecules (9). The first direct evidence for endogenous opioids in brain extracts was provided in 1975 when two pentapeptides were purified that differed only in the carboxyl terminal amino acids (10) (Table 1). These peptides were called methionine- (Met-) and leucine- (Leu-) enkephalin, from the Greek term meaning "in the head."... 

Binding of the basic peptide to terminal polymer carboxylate groups may play a significant role in the release mechanism (124). 

Peptides are named for the number of amino acid residues present, and as derivatives of the carboxyl terminal residue. The primary structure of a peptide is its amino acid sequence, starting from the amino-terminal residue. 

Figure 5-8. Domain structure. Protein kinases contain two domains. The upper, amino terminal domain binds the phosphoryl donor ATP (light blue). The lower, carboxyl terminal domain is shown binding a synthetic peptide substrate (dark blue).

Figure 7-7. Catalysis by chymotrypsin. The charge-relay system removes a proton from Ser 195, making it a stronger nucleophile. Activated Ser 195 attacks the peptide bond, forming a transient tetrahedral intermediate. Release of the amino terminal peptide is facilitated by donation of a proton to the newly formed amino group by His 57 of the charge-relay system, yielding an acyl-Ser 195 intermediate. His 57 and Asp 102 collaborate to activate a water molecule, which attacks the acyl-Ser 195, forming a second tetrahedral intermediate. The charge-relay system donates a proton to Ser 195, facilitating breakdown of tetrahedral intermediate to release the carboxyl terminal peptide .

Other antibiotics inhibit protein synthesis on all ribosomes (puromycin) or only on those of eukaryotic cells (cycloheximide). Puromycin (Figure 38—11) is a structural analog of tyrosinyl-tRNA. Puromycin is incorporated via the A site on the ribosome into the carboxyl terminal position of a peptide but causes the premature release of the polypeptide. Puromycin, as a tyrosinyl-tRNA analog, effectively inhibits protein synthesis in both prokaryotes and eukaryotes. Cycloheximide inhibits peptidyltransferase in the 60S ribosomal subunit in eukaryotes, presumably by binding to an rRNA component. 

There are two main classes of proteolytic digestive enzymes (proteases), with different specificities for the amino acids forming the peptide bond to be hydrolyzed. Endopeptidases hydrolyze peptide bonds between specific amino acids throughout the molecule. They are the first enzymes to act, yielding a larger number of smaller fragments, eg, pepsin in the gastric juice and trypsin, chymotrypsin, and elastase secreted into the small intestine by the pancreas. Exopeptidases catalyze the hydrolysis of peptide bonds, one at a time, fi"om the ends of polypeptides. Carboxypeptidases, secreted in the pancreatic juice, release amino acids from rhe free carboxyl terminal, and aminopeptidases, secreted by the intestinal mucosal cells, release amino acids from the amino terminal. Dipeptides, which are not substrates for exopeptidases, are hydrolyzed in the brush border of intestinal mucosal cells by dipeptidases. 

A number of peptide hormones have a carboxyl terminal amide which is derived from a glycine terminal residue. This glycine is hydroxylated on the a-carbon by a copper-containing enzyme, peptidylglycine hydroxylase, which, again, requires ascorbate for reduction of Cu ". ... 

Notice that this dipeptide is also an amino acid because the molecule retains an amine group at one end and a carboxyl group at the other end. Consequently, an additional amino acid can add to either end of a dipeptide to form a new peptide that also has an amine terminal group at one end and a carboxyl terminal group at its other end. Figure 13-34 shows the peptide that results from addition of another alanine molecule at the amine end and a cysteine molecule at the carboxyl end of the Ala-Gly dipeptide. 

For carboxyl terminal determination of peptides by means of CDI the terminal carboxylic acid group of the peptide is selectively reduced with sodium dihydrobis(2-methoxy-ethoxy)aluminate to an alcohol. Subsequent conversion of the amino alcohol moiety with CDI yields an 7V-acyl-2-oxazolidone derivative, from which the oxazolidone unit can be easily removed and characterized.[56]... 

S-Acylation and Plasma Membrane Targeting of the Farnesylated Carboxyl-Terminal Peptide of N-Ras in Mammalian Fibroblasts, H. Schroeder, R. Leventis, S. Rex, M. Schelhaas, E. Nagele, H. Waldmann, J. R. Silvius, Biochemistry 1997, 36,13102-13109. 

The hydrophobic peptide segments of El and E2, which attach the spike protein to the lipid bilayer, can be localized on the polypeptide chains by a mapping procedure first used by Dintzis (1961) to show that the synthesis of polypeptide chains begins at the amino-terminal end. The hydrophobic stubs left in the viral membrane after protease treatment are found at the carboxyl-terminal ends of both the El and the E2 polypeptides (Garoff and Sdderlund, 1978). 

The normal internalization of the wild-type receptor, defined as a loss of cell surface receptors (measured by decreased maximal binding or B ), was unaffected for the desensitization-deficient Thr mutant (see Fig. 6.4C,D) but may have been affected when distal carboxyl terminal residues were mutated (see Fig. 6.3). Therefore some, although not all, GPCRs show radical dissociation between desensitization and internalization. This is found not only in the dopamine Dj receptor (122) but also in the N-formyl peptide (134), the CBl cannabinoid (17), and the M2 muscarinic (155) receptors. 

Substance P belongs to the tachykinin family of peptides, which share the common carboxyl terminal sequence Phe-X-Gly-Leu-Met. 

In the brain, processing of the precursor leads primarily to the formation of NT and neuromedin N these are released together from nerve endings. In the gut, processing leads mainly to the formation of NT and a larger peptide that contains the neuromedin N sequence at the carboxyl terminal. Both peptides are secreted into the circulation after ingestion of food. Most of the activity of NT is mediated by the last six amino acids, NT(8-13). 

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