Peptides polypeptide synthesis

The major disadvantage of solid-phase peptide synthesis is the fact that ail the by-products attached to the resin can only be removed at the final stages of synthesis. Another problem is the relatively low local concentration of peptide which can be obtained on the polymer, and this limits the turnover of all other educts. Preparation of large quantities (> 1 g) is therefore difficult. Thirdly, the racemization-safe methods for acid activation, e.g. with azides, are too mild (= slow) for solid-phase synthesis. For these reasons the convenient Menifield procedures are quite generally used for syntheses of small peptides, whereas for larger polypeptides many research groups adhere to classic solution methods and purification after each condensation step (F.M. Finn, 1976). 

Solid phase peptide synthesis (Section 27 18) Method for peptide synthesis m which the C terminal ammo acid is co valently attached to an inert solid support and successive ammo acids are attached via peptide bond formation At the completion of the synthesis the polypeptide is removed from the support... 

Polypeptide Synthesis and Analysis. Sihca or controUed-pore glass supports treated with (chloromethyl)phenylethyltrimethoxysilane [68128-25-6] or its derivatives are replacing chloromethylated styrene—divinylbenzene (Merrifield resin) as supports in polypeptide synthesis. The sdylated support reacts with the triethyl ammonium salt of a protected amino acid. Once the initial amino acid residue has been coupled to the support, a variety of peptide synthesis methods can be used (34). At the completion of synthesis, the anchored peptide is separated from the support with hydrogen bromide in acetic acid (see Protein engineering Proteins). 

ELPs can be produced via chemical synthesis and biosynthetically. For chemical synthesis via solid phase peptide synthesis, the attainable polymer length is limited, and if long polymers with a defined length are required then the biosynthetic approach is more appropriate. An advantage of chemical synthesis is, however, that it enables the facile introduction of functional residues in the polypeptide [27]. 

DMAP has been found to improve the coupling reaction in solid phase peptide synthesis (4). Polypeptides synthesized via the DMAP-DCC method were found to be of higher purity compared to other methods of synthesis. In polymer chemistry, DMAP has been used for hardening of resins and in the synthesis of polyurethanes, (5) polycarbonates, (6) and polyphenyleneoxides (7) ... 

Moreover, if the average yield per step decreases only slightly, let us say down to 85%, the overall yield of the convergent synthesis is still quite acceptable -37%-, but now the overall yield of the linear synthesis would be only 0.004%. It is clear, therefore, that for polypeptides of any complexity and for proteins, linear syntheses in solution are not practicable even if the yields of each step are kept high. However, solid-phase peptide synthesis can be quite efficient. This is because solid-phase synthesis represents an improvement in linear methodology which has, as yet, not found an equivalent in convergent methods [17]. 

DKPs are simple and easy to obtain and are quite common by-products of synthetic, spontaneous, and biological formation pathways. DKP formation has been well documented as side reactions of solid-phase and solution-phase peptide synthesis. In addition, DKPs have been shown to be decomposition products of various peptides, proteins, and other commercial pharmaceuticals. Cyclic dipeptides were found to be present in solutions of human growth hormone, bradykinin, histerlin, and solutions of agents within the classes of penicillins and cephalosporins. " DKPs are also enzymatically synthesized in several protists and in members of the plant kingdom. Hydrolysates of proteins and polypeptides often contain these compounds and they are commonly isolated from yeasts, lichens, and fungi. ... 

The methods of peptidic synthesis, in the liquid phase as well as in the solid phase, have led to the preparation of numerous polypeptides that contain a fluorinated amino acid. Most of the examples concern peptidic hormones and neuropeptides, with replacement of either (1) a phenylalanine (or of a tyrosine) by an analogue containing a... 

This equation is not intended to imply a mechanism for peptide synthesis. The equilibrium position for this reaction in an aqueous solution favors the free amino acids rather than the peptide. Therefore, both biological and laboratory syntheses of peptides usually do not involve a simple splitting out of water. Since the dipeptide of Eq. 2-11 still contains reactive carboxyl and amino groups, other amino acid units can be joined by additional peptide linkages to form polypeptides. These range from short-chain oligomers to polymers of from 50 to several thousand amino acid units, the proteins.75-77... 

Shenderovich, M., Biopolymers, (1997) 43,219. 01 Schroder, E. Lubke, K., The Peptides Methods of Peptide Synthesis The Peptides Synthesis, Occurrence, and Action of Biologically Active Polypeptides, Academic New York, (1966) Vol. II. 

Exercise 25-22 Suppose there is 1% formation in each step of the wrong isomer of the acylating component in an otherwise quantitative 100-step peptide synthesis. What is the yield of the desired polypeptide isomer ... 

Polypeptide formation involves a repetition of the process involved in peptide synthesis. 

In solid phase peptide synthesis, polypeptides are chemically synthesized by addition of free amino acids to a tethered peptide. To prevent unwanted reactions, the a-amino group and reactive side chain groups of the free amino acids are chemically protected or blocked, and then deprotected or deblocked once the amino acid is attached to the growing polypeptide chain. 

Peptide synthesis Polypeptides can be chemically synthesized by covalently linking amino acids to the end of a growing polypeptide chain. In solid phase peptide synthesis the growing polypeptide chain is covalently anchored at its C-terminus to an insoluble support such as polystyrene beads. The next amino acid in the sequence has to react with the free a-amino group on the tethered peptide, but it has a free a-amino group itself which will also react. To overcome this problem the free amino acid has its a-amino group chemically protected (blocked) so that it does not react with other molecules. Once the new amino acid is coupled, its now N-terminal a-amino group is deprotected (deblocked) so that the next... 

Pessi et al. 68 prepared a different multiple antigen peptide employing the continuous-flow polypeptide procedure 69 for the solid-phase peptide synthesis. The resultant one-directional, octaantigen, polypeptide cascade 37 is depicted in Figure 4.2 and was characterized by gel permeation chromatography (GPC), FAB MS, and amino acid ratio analysis. 

Figure 4.2. Octaantigen polypeptide 37 was prepared via solid phase peptide synthesis.

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