Chain peptide

Proteins consist of large numbers of amino-acids joined by the p>eptide link —CO —NH — into chains, as shown in the diagram, where R and R" are amino-acid residues. These chains are called peptides and may be broken into smaller chains by partial hydrolysis (see peptides). Proteins may contain more than one peptide chain thus insulin consists of... 

The N-to-C assembly of the peptide chain is unfavorable for the chemical synthesis of peptides on solid supports. This strategy can be dismissed already for the single reason that repeated activation of the carboxyl ends on the growing peptide chain would lead to a much higher percentage of racemization. Several other more practical disadvantages also tend to disfavor this approach, and acid activation on the polymer support is usually only used in one-step fragment condensations (p. 241). 

The amino add analysis of all peptide chains on the resins indicated a ratio of Pro Val 6.6 6.0 (calcd. 6 6). The peptides were then cleaved from the resin with 30% HBr in acetic acid and chromatogra phed on sephadex LH-20 in 0.001 M HCl. 335 mg dodecapeptide was isolated. Hydrolysis followed by quantitative amino acid analysis gave a ratio of Pro Val - 6.0 5.6 (calcd. 6 6). Cycll2ation in DMF with Woodward s reagent K (see scheme below) yielded after purification 138 mg of needles of the desired cyc-lododecapeptide with one equiv of acetic add. The compound yielded a yellow adduct with potassium picrate, and here an analytically more acceptable ratio Pro Val of 1.03 1.00 (calcd. 1 1) was found. The mass spectrum contained a molecular ion peak. No other spectral measurements (lack of ORD, NMR) have been reported. For a thirty-six step synthesis in which each step may cause side-reaaions the characterization of the final product should, of course, be more elaborate. 

Only the N terminal amide bond is broken m the Edman degradation the rest of the peptide chain remains intact It can be isolated and subjected to a second Edman procedure to determine its new N terminus We can proceed along a peptide chain by beginning with the N terminus and determining each ammo acid m order The sequence is given directly by the structure of the PTH derivative formed m each successive degradation... 

Section 27 20 The folding of a peptide chain is its tertiary structure The tertiary struc ture has a tremendous influence on the properties of the peptide and the biological role it plays The tertiary structure is normally determined by X ray crystallography... 

The discovery of nbozymes (Section 28 11) in the late 1970s and early 1980s by Sidney Altman of Yale University and Thomas Cech of the University of Colorado placed the RNA World idea on a more solid footing Altman and Cech independently discovered that RNA can catalyze the formation and cleavage of phosphodiester bonds—exactly the kinds of bonds that unite individual ribonucleotides in RNA That plus the recent discovery that ribosomal RNA cat alyzes the addition of ammo acids to the growing peptide chain in protein biosynthesis takes care of the most serious deficiencies in the RNA World model by providing precedents for the catalysis of biologi cal processes by RNA... 

Transcription (Section 28 11) Construction of a strand of mRNA complementary to a DNA template Transfer RNA (tRNA) (Section 28 11) A polynucleotide of n hose that is bound at one end to a unique amino acid This ammo acid is incorporated into a growing peptide chain Transition state (Section 3 1) The point of maximum energy in an elementary step of a reaction mechanism Translation (Section 28 12) The reading of mRNA by van ous tRNAs each one of which is unique for a particular ammo acid... 

Peptide chain with two cystine residues (R = -CHgSH)... 

These methodologies have been reviewed (22). In both methods, synthesis involves assembly of protected peptide chains, deprotection, purification, and characterization. However, the soHd-phase method, pioneered by Merrifield, dominates the field of peptide chemistry (23). In SPPS, the C-terminal amino acid of the desired peptide is attached to a polymeric soHd support. The addition of amino acids (qv) requires a number of relatively simple steps that are easily automated. Therefore, SPPS contains a number of advantages compared to the solution approach, including fewer solubiUty problems, use of less specialized chemistry, potential for automation, and requirement of relatively less skilled operators (22). Additionally, intermediates are not isolated and purified, and therefore the steps can be carried out more rapidly. Moreover, the SPPS method has been shown to proceed without racemization, whereas in fragment synthesis there is always a potential for racemization. Solution synthesis provides peptides of relatively higher purity however, the addition of hplc methodologies allows for pure peptide products from SPPS as well. 

Insulin and Amylin. Insulin is a member of a family of related peptides, the insulin-like growth factors (IGFs), including IGF-I and IGF-II (60) and amylin (75), a 37-amino acid peptide that mimics the secretory pattern of insulin. Amylin is deficient ia type 1 diabetes meUitus but is elevated ia hyperinsulinemic states such as insulin resistance, mild glucose iatolerance, and hypertension (33). Insulin is synthesized ia pancreatic P cells from proinsulin, giving rise to the two peptide chains, 4. and B, of the insulin molecule. IGF-I and IGF-II have stmctures that are homologous to that of proinsulin (see INSULIN AND OTHER ANTIDIABETIC DRUGS). 

Cellular protein biosynthesis involves the following steps. One strand of double-stranded DNA serves as a template strand for the synthesis of a complementary single-stranded messenger ribonucleic acid (mRNA) in a process called transcription. This mRNA in turn serves as a template to direct the synthesis of the protein in a process called translation. The codons of the mRNA are read sequentially by transfer RNA (tRNA) molecules, which bind specifically to the mRNA via triplets of nucleotides that are complementary to the particular codon, called an anticodon. Protein synthesis occurs on a ribosome, a complex consisting of more than 50 different proteins and several stmctural RNA molecules, which moves along the mRNA and mediates the binding of the tRNA molecules and the formation of the nascent peptide chain. The tRNA molecule carries an activated form of the specific amino acid to the ribosome where it is added to the end of the growing peptide chain. There is at least one tRNA for each amino acid. 

Properties and Structure. a -Acid glycoprotein (a -AGP) has a molecular mass of about 41,000 and consists of a peptide chain having 181 amino acid residues and five carbohydrate units (14,15). Two cystine disulfide cross-linkages connect residues 5 and 147 and residues 72 and 164. The carbohydrate units comprise 45% of the molecule and contain siaUc acid, hexosamine, and neutral hexoses. In phosphate buffer the isoelectric point of the... 

Peptidoplycans (14,16) are the primary component of bacterial cell walls. They consist of a heteropolysaccharide called murein cross-linked with short peptide chains. 

As a result of the en2ymatic degradation of proteins, key indexes change, ie, protein solubiUty indexes (PSI), peptide chain length (PCL), and protein solubihty in 0.8 Af TCA (TCA-index) (Fig. 14). Unpleasant bitterness was once a problem for some protein hydroly2ates. This problem can now be overcome by proper selection of the reaction parameters and the en2ymes used. 

Fig. 14. Time dependence of key indexes during en2ymatic hydrolysis (a) degree of hydrolysis (DH) (b) peptide chain length (PCL) (soluble peptides) (c)...

A disulfide bond (yellow) links the two peptide chains. (Courtesy of A.l. Wilson.)... 

Proline is the only amino acid in Table 27.1 that is a secondary amine, and its presence in a peptide chain introduces an amide nitrogen that has no hydrogen available for hydrogen bonding. This disrupts the network of hydrogen bonds and divides the peptide into two separate regions of a helix. The presence of proline is often associated with a bend in the peptide chain. 

Pleated p sheet (Section 27.19) Type of protein secondary structure characterized by hydrogen bonds between NH and C=0 groups of adjacent parallel peptide chains. The individual chains are in an extended zigzag conformation. 

Transfer RNA (tRNA) (Section 28.11) A polynucleotide of ri-bose that is bound at one end to a unique amino acid. This amino acid is incorporated into a growing peptide chain. 

Weak intramolecular interactions between sulfur or selenium and nitrogen are a recurrent phenomenon in large biomolecules. They may occur in the same residue or between neighbours of a peptide chain. The formation of four- or five-membered rings of the types 15.1 and 15.2, respectively, is most common. A feature that is unique to proteins is the participation of sulfur atoms in bifurcated N S N contacts. 

Cell wall Peptidoglycan a rigid framework of polysaccharide cross-linked by short peptide chains. Some bacteria possess a lipopolysaccharide- and protein-rich outer membrane. Mechanical support, shape, and protection against swelling in hypotonic media. The cell wall is a porous nonselective barrier that allows most small molecules to pass. 

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. 

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