Synthesis of Peptides and Proteins

Solid-phase peptide synthesis offers a fast and convenient route for many peptides when isotope-enriched compounds are not required. Classical synthesis additionally permits the use of non-natural amino acids and allows site-specific isotope labeling. Although Fmoc protected 15N-labeled amino adds are commercially available, the cost of such synthesis is usually prohibitive, and the peptides from chemical synthesis require perdeuterated detergents and unfortunately exclude investigation of internal dynamics through measurement of 15N relaxation. 

Smaller peptides are difficult to overexpress in E. coli and are additionally degraded in cells. These problems are commonly circumvented if fusion peptides are used from 

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A number of reactions of amino acids have become important in recent years because they are essential to the degradation, sequencing, and chemical synthesis of peptides and proteins. These reactions are discussed in Chapter 5. 

Lloyd-Williams P, Albericio F, Giralt E (1997) Chemical approaches to the synthesis of peptides and proteins. CRC, Boca Raton... 

Lloyd-Williams, R, Albericio, F. and Giralt, E. (1997) Chemical Approaches to the Synthesis of Peptides and Proteins. 367pp. CRC Press. The main focus is on large molecules, with 1343 references. 

Y Nishiuchi, H Nishio, J Bodi, T Kimura. Combined solid-phase and solution approach for the synthesis of peptides and proteins. J Pept Sci 6, 84, 2000. 

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... 

R. B. Merrifield, Methods. Enzymol. 289 3 (1997) K. B. Merrifield, in Peptides Synthesis, Structure, and Applications, B. Gutte, ed., Academic Press, San Diego, 1995, p. 93 Atherton and R. C. Sheppard, Solid Phase Peptide Synthesis, IRL Press, Oxford, U.K., 1989 P. Lloyd-Williams, F. Albericio, and E. Giralt, Chemical Synthesis of Peptides and Proteins, CRC Press, Boca Raton, Florida, 1997. 

This expresses the feelings of others in this field, and even today most syntheses have been undertaken mainly to examine the new methodology at hand and to test its limits. The second objective then becomes the application of the technology to answer important chemical and biological questions through the chemical synthesis of peptides and proteins. 

It is of some interest to note that 24 of the starting fragments were prepared by solid-phase methods in order to simplify and accelerate the synthesis. This confirms what we have believed for a long time, i.e. that the various approaches (chemical, enzymatic, and biological) to the synthesis of peptides and proteins are not mutually exclusive but, rather, they can complement one another when judiciously selected for the particular problem at hand. 

S. B. H. Kent, Chemical synthesis of peptides and proteins, Annu. Rev. Biochem. 547 957... 

The solid phase method (8S) for the synthesis of peptides and proteins has been used in the synthesis of a large number of analogs of nuclease. 

The foregoing typical results clearly illustrate another very important application of the polyethyleneglycol support method for the synthesis of peptides and protein sequences. The unique suitability of this linear, soluble macromolecular support with optimum hydrophilicity-hydrophobicity balance for the conformational analysis of the bound peptides originates from the peculiar conformational properties of the polymer chain. 

Yan, L. Z. and Dawson, P. E. (2001) Synthesis of peptides and proteins without cysteine residues by native chemical ligation combined with desulfurization. J. Am. Chem. Soc. 123, 526-533. 

In principle, the synthesis of peptides and proteins is based on a rather simple chemical reaction, i.e. polycondensation via anoide bond formation of natural proteinogenic and... 

Table 1 Main Protection Schemes Presently Used for Synthesis of Peptides and Proteins in Solution and on Solid Support or by Convergent StrategiesI - ...

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