Synthesis of peptide

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 synthesis of peptide antagonists has greatiy aided in the development of knowledge of other neuropeptide systems as well. 

Synthesis of Peptide. There is continual progress ia the improvement of instmments and reagents for peptide synthesis, especially "soHd phase polymerization" (90) (see Proteins). This method is suitable for the synthesis of peptides with 20 30 amino acid units. 

Peptide Synthesis. The literature on the enzymatic synthesis of peptides is enormous (120—124). Here the basic principles that govern peptide synthesis are illustrated and recent trends in this area reviewed. 

During the synthesis of peptides that contain 4-methoxybenzyl-protected cysteine residues, sulfoxide formation may occur. These sulfoxides, when treated with HF/ anisole, form thiophenyl ethers that cannot be deprotected therefore, the peptides should be subjected to a reduction step prior to deprotection. ... 

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. 

R. B. Merrifield (Rockefeller, New York) development of methodology for the synthesis of peptides on a solid matrix. 

The smooth conversion of the enol acetate (151) into an A -acyl derivative (152) under extremely mild conditions points to the high acylating capacity of these esters. This cleavage of isoxazolium salts is also caused by other anions of carboxylic acids, and thus they can be readily converted to reactive enol esters. A very convenient and specific synthesis of peptides due to Woodward et is based on... 

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. 

Robert Bruce Merrifield (1921-2006) was born in Fori Worth, Texas, anti received his Ph.D. at the University oi California, Los Angeles, in 1949. He then joined the faculty at the Rockefeller Institute, where he remained until his death. In 1984, he was awarded the Nobel Prize in chemistry for his development of methods for the automated synthesis of peptides. 

Although the solid-phase technique was first developed for the synthesis of peptide chains and has seen considerable use for this purpose, it has also been used to synthesize chains of polysaccharides and polynucleotides in the latter case, solid-phase synthesis has almost completely replaced synthesis in solution. The technique has been applied less often to reactions in which only two molecules are brought together (nonrepetitive syntheses), but many examples have been reported. 

Jones J., The Chemical Synthesis of Peptides—International Series of Monographs on Chemistry, Oxford University Press, Oxford, 1994. 

Tab. 2.1 Representative list of N-protected / -amino acids 14 used in the synthesis of/ -peptides...

Scheme 11. Synthesis of peptide containing primary phosphine 23...

Scheme 12. Synthesis of peptide containing hydroxymethyl phosphane 25...

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

Mei Y, Beers KL, Byrd HCM et al (2004) Solid-phase atrp synthesis of peptide- polymer hybrids. J Am Chem Soc 126 3472-3476... 

Figure 12.2 A hypothetical synapse where co-existence of peptides and classical transmitters occurs. A is a classical transmitter whereas B and C are peptides. The slow synthesis of peptides and the need for axonal transport may mean that in active neurons, the classical transmitter may be released under all conditions, but the peptide(s) may require higher intensities of stimulation for release and be depleted if the neuron continues to fire for long periods. Competition for peptidases can lead to changes in levels of two co-released peptides. At the postsynaptic site, the receptor mechanisms of the co-existing transmitters can also produce complex changes in neuronal activity...

Watts, P., Wiles, C., Haswell, S. )., PoMBO-ViLiAE, E., Solution phase synthesis of peptides using micro reactors. Tetrahedron 58, 27 (2002) 5427-5439. 

Palchetti I, Mascini M (2005) Electrochemical Adsorption Technique for Immobilization of Single-Stranded Oligonucleotides onto Carbon Screen-Printed Electrodes. 261 27-43 Pascal R, Boiteau L, Commeyras A (2005) From the Prebiotic Synthesis of a-Amino Acids Towards a Primitive Translation Apparatus for the Synthesis of Peptides. 259 69-122 Paulo A, see Santos I (2005) 252 45-84 Perez EM, see Leigh DA (2006) 265 185-208 Perret F, see Coleman AW (2007) 277 31-88 Perron H, see Coleman AW (2007) 277 31-88 Pianowski Z, see Winssinger N (2007) 278 311-342 Piestert F, see Gansauer A (2007) 279 25-52... 

Burke TR Jr, Smyth M, Nomizu M, Otaka A, Roller PP. Preparation of fluoro- and hydroxy-4-(phosphonomethyl)-D,L-phenylalanine suitably protected for a solid-phase synthesis of peptides containing hydrolytically stable analogues of O-phosphotyrosine. J Org Chem 1993 58 1336-1340. 

Matsueda GR, Stewart JM. A p-methylbenzhydrylamine resin for improved solid-phase synthesis of peptides amides. Peptides 1981 2 45-50. 

Henkel B, Zeng W, Bayer E. 9-Hydroxy-9-(4-carboxyphenyl)xanthene- a new linker for the synthesis of peptide amides. Tetrahedron Lett 1997 38 3511-3512. 

Breipohl G, Knolle J, Stuber W. Synthesis and application of acid labile anchor groups for the synthesis of peptide amides by Fmoc-solid-phase peptide synthesis. Int J Peptide Protein Res 1989 34 262-267. 

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