Laboratory Synthesis of Peptides

Ethers with a tertiary, benzylic, or allylic group cleave by an S l or FI mechanism because these substrates can produce stable intermediate carbocations. These reactions are often fast and take place at moderate temperatures. fcrf-Butyl ethers, for example, react by an El mechanism on treatment with trifluoroacetic acid at 0 °C. We ll see in Section 26.7 that the reaction is often used in the laboratory synthesis of peptides. 

Amino Adds, Peptides, and Proteins 26.7 Laboratory Synthesis of Peptides Active Figure 26.4 Mechanism of Amide Formation Using Dicydohexylcarbodiimide (page 1151) Coached Tutorial Problem Reactions Used in Synthesis of Peptides (page 1151)... 

Synthesis. In contrast to pituitary hormones, which usually can be obtained in pure form only after extraction from animal tissues, brain oligopeptides are readily available because of their small size. The synthetic repHca represents the most economical and readily accessible source for the oligopeptides. Two techniques are available for laboratory synthesis of oligopeptides, ie, solution chemistry and soHd-phase peptide synthesis (SPPS). 

We ll see in Section 26.7 that this DCC-induced method of amide formation is the key step in the laboratory synthesis of small proteins, or peptides. For instance, when one amino acid with its NH2 rendered unreactive and a second... 

In the synthesis of peptides and proteins, recognition of the constituent aminoacids is almost immediate however, the realisation of the synthesis in the laboratory may be one of the most arduous tasks which the synthetic organic chemist faces. The molecular magnitude and the strong polarity which tends to make the reaction intermediates very insoluble, as well as the problem of conservation of... 

The technique of using proteases in peptide synthesis has been carefully reviewed (60,61) and the technology is advanced to the state that commercially prepared kits for this type of synthesis are available. Nevertheless, due to the well defined methodological routines devised for generjd synthesis of peptides for laboratory use, the standard chemical approaches are likely to remain the methods of choice. 

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... 

The synthesis of peptides of known sequence in the laboratory is extremely important to biochemical research. For example, we might want to know how the effects of a peptide hormone are altered by replacement of one amino acid in a particular position by another. The synthetic methods must be precise294-298 and because there are so many steps the yield should... 

The problems involved in peptide syntheses are of much practical importance and have received considerable attention. The major difficulty in putting together a chain of say 100 amino acids in a particular order is one of overall yield. At least 100 separate synthetic steps would be required and, if the yield in each step were equal to n x 100%, the overall yield would be (n1U0 x 100%). If the yield in each step were 90%, the overall yield would be only 0.003%. Obviously, a practical laboratory synthesis of a peptide chain must be a highly efficient process. The extraordinary ability of living cells to achieve syntheses of this nature, not of just one but of a wide variety of such substances, is truly impressive. 

The apparatus routinely used in this laboratory for the manual synthesis of peptides consists of a flask attached to a glass manifold that can support up to four sintered funnels, thereby permitting the simultaneous synthesis of up to four peptides. The side arm of the flask is attached to a vacuum pump to allow for solvents to be aspirated from each funnel. The manifold also contains valves... 

First the general structure and chemistry of the amino acids is presented. Then several methods that can be used to prepare them in the laboratory are discussed. After an introduction to the structure of peptides and proteins, chemical methods that can be used to determine the amino acid sequence in proteins are presented. Next, the synthesis of peptides in the laboratory is introduced. Finally, the three-dimensional structure of proteins and the mechanism of action of enzymes are briefly addressed. 

Understand the laboratory synthesis of a peptide in solution or by the solid phase method. (Problems 26.35 and 26.36)... 

Synthesis of peptides in solution is currently practiced in very few laboratories, or is applied in the case of large-scale peptide synthesis. Multiple solution... 

---