Peptide link

Peptide is the name assigned to short polymers of amino acids. Peptides are classified by the number of amino acid units in the chain. Each unit is called an amino acid residue, the word residue denoting what is left after the release of HgO when an amino acid forms a peptide link upon joining the peptide chain. Dipeptides have two amino acid residues, tripeptides have three, tetrapeptides four, and so on. After about 12 residues, this terminology becomes cumbersome, so peptide chains of more than 12 and less than about 20 amino acid residues are usually referred to as oligopeptides, and, when the chain exceeds several dozen amino acids in length, the term polypeptide is used. The distinctions in this terminology are not precise. 

One of the most successful conjugate polymer systems was developed by Duncan and Kopecek (25). The polymer carrier used in their system is poly [N(2-hydroxypropyl) methacrylamide] a biocompatible polymer that was originally developed as a plasma extender. They have evaluated a number of polymer conjugated drugs for cancer chemotherapy with interesting results. The attachment of the drug is through a peptidyl spacer pendent to the polymer backbone. These peptides links are stable in aqueous media but are readily hydrolyzed intracellularly... 

A Battersby, JC Robinson. Studies on the specific fission of peptide links. Part 1. The rearrangement of aspartyl and glutamyl peptides. J Chem Soc 259, 1955. 

The classification adopted by the Nomenclature Committee (NC) of the International Union of Biochemistry and Molecular Biology (IUBMB) divides peptidases into classes and subclasses according to the positional specificity in the cleavage of the peptide link of the substrate. The last publication of the complete printed version of the Enzyme Nomenclature was in 1992 [1][2], but a constantly updated version with supplements is available on the World Wide Web at http //www.chem.qmul.ac.uk/iubmb/enzyme/. Similarly, all available Protein Data Bank (PDB) entries classified as recommended by the NC-IUBMB can be found on the WWW at http //www.bio-chem.ucl.ac.uk/bsm/enzymes/. 

Fig. 4. Capping units (a) bonding through peptide links, (b) to ring-carbon or ring-nitrogen, (c) to give hexadentate hydroxypyridinones, (d) such as 21, tren(3,2-hopo)3.

Protection of the peptide link is afforded by the addition of hydrogenbonding compounds, such as benzaldehyde ... 

The proteasome is a very large complex of at least 50 subunits. It is present in a wide variety of tissues and can constitute up to 1% of soluble protein in a cell. The catalysis occurs within the central core of the molecule and ATP hydrolysis is required to drive the protein into the core. Before the complex can break down proteins, the latter must first have been tagged by complexing with ubiquitin, a peptide of molecular mass 8.5 kDa. This attachment requires three enzymes and the hydrolysis of ATP and it results in a peptide link between the carboxylic group at the C-terminus of ubiquitin and the NH2 of a lysine side-chain in the condemned protein. Several ubiquitin molecules are attached to a single lysine so that a chain of four or more ubiquitin molecules is formed (Figure 8.2). It is. 

There are several steps in the absorption of vitamin B. In the stomach and lumen of the small intestine it is hydrolysed from its (peptide) links with the proteins of which it is a component. It then attaches to gastric intrinsic factor, which is a glycoprotein of molecular mass about 50 000 kDa, to form a complex. This protects the vitamin from being damaged by acid in the stomach. The complex is carried into the ileum, where it binds to a receptor on the surface of the absorptive cells and is released from the intrinsic factor within the absorptive cell, hi the portal venous blood, it is transported to the liver bound to the vitamin B 12-binding protein, which also protects the vitamin. 

Many medicinally useful peptides have cyclic structures. Cyclization may result if the amino acids at the two termini of a linear peptide link up to form another peptide bond. Alternatively, ring formation can very often be the resnlt of ester or amide linkages that utilize side-chain functionalities (CO2H, NH2, OH) in the constituent amino acids. 

This was shown to occur because silica binds to the same features in polypeptides that polyphenols do (peptidically linked proline Siebert and Lynn, 1997b) (see the concept in Fig. 2.21). In contrast, in unstabilized apple juice, silica removes only on the order of 20% of the HA protein... 

The observed and fitted potentials in the region of a peptide link are compared in Fig. 8.6. Except for the inner regions, the agreement is satisfactory. In particular, the pronounced negative areas in the proximity of the oxygen atom are well reproduced. 

FIG. 8.6 Electrostatic potential maps in the region of one of the peptide links in iV-acetyl-a,/f-dehydrophenylalanine methylamide. (a) Observed, (b) From net charges fitted to the potential. Contours are at 0.05 eA 1 (1 eA) 1 = 332.1 kcal mol ). Zero and negative contours are dashed lines. Source Ghermani et al. (1993). 

For the hydrolysis of peptides linked to resins, the release of the C-terminal amino acid is strongly dependent upon the type of resin and amino acid residue. For this purpose the use of propanoic acid/12M HC1 (1 1 )[6 is recommended. More studies, however, indicate hydrolysis with TFA/12M HC1 (1 3) at 160°C is more appropriate since quantitative release of the most stable Phe residue from benzhydrylamine- (BHA-), 4-methylbenzhydrylamine-(pMeBHA-), and 4-(hydroxymethyl)phenylacetamidomethyl-resins occurs in 20, 6, and 5 h, respectively, compared to the 30,18, and 18h required with propanoic acid/12M HC1 (1 1)) ... 

D-Xylosy]-L-serine as a Carbohydrate-peptide Linking Moiety...434... 

Bufotoxins These are steroidal bufagins, usually linked via an hydroxyl suberic acid which is, in turn, bound by a peptide link to arginine. 

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