Synthesis of protected peptide fragments

Solid phase synthesis of protected peptide fragments 

In general, protected peptide fragments of any length can be used in the condensation reaction, if they are of satisfactory purity and solubility. Usually, fragments of up to 15 amino acids in length are used, because of their simpler pinification by RP-HPLC compared with the longer peptides. The solubility of protected peptide acids is independent of their length. 

Owing to the lack of valuable information in the literature, we performed experiments to determine the suitability of the various amino acids as C- and N-terminal amino acids of the protected fragments. We found that in terms of racemization and condensation rates, Gly, Pro, Lys(Boc), and Glu(tBu) are preferred as the C-terminal amino acid and Gly, Ala, Asp(iBu), Glu(tBu), Lys(Boc), and Ser(tBu) as the N-terminal. In general, the condensation efficiency depends more on the natme of the resin-bound N-component thtm on that of the C-component. 

2 Synthesis of protected peptide fragments 2.2.1 Esterification of the first amino acid on 2-chlorotrityl chloride resin 

The esterification of Fmoc-amino acids and peptides to CLTR proceeds rapidly, in high yield, and without racemization Protocol 1). Nevertheless, the amino acid-resin bond is extremely sensitive until the Fmoc-function has 

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Wang SS. p-Alkoxybenzyl alcohol resin and p-alkoxybenzyloxycarbonylhy-drazide resin for solid-phase synthesis of protected peptide fragments. J Am Chem Soc 1973 95 1328-1333. 

Rink H. Solid-phase synthesis of protected peptide fragments using a trialkoxy diphenyl methylester resin. Tetrahedron Lett 1987 28 3787-3790. 

Rink, H. Solid-Phase Synthesis of Protected Peptide Fragments Using a Trialkoxydiphenyl-Methylester Resin, Tetrahedron Lett. 1987, 28, 3787-3790. 

Wang, S.-S. p-Alkoxybenzyl Alcohol Resin and p-Alkoxybenzyloxycar-bonylhydrazide Resin for Solid Phase Synthesis of Protected Peptide Fragments, J. Am. Chem. Soc. 1973, 95, 1328-1333. 

Dialkoxy- and trialkoxybenzyl esters are even more acid-labile than the Wang linker, and can, for example, be cleaved with dilute TFA, acetic acid, or hexafluoroiso-propanol without simultaneous acidolysis of Boc groups. These linkers thus enable the solid-phase synthesis of protected peptide fragments or other acid-sensitive products [33]. 

Blankemeyer-Menge, B. and Frank, R. (1988) Simultaneous multiple synthesis of protected peptide fragments on ally -functionalized cellulose disc supports. Tetrahedron Lett. 29, 5871-5874. 

Scheme 10 Synthesis of Protected Peptide Fragments Corresponding to the Sequence 1-9 of S. solfataricus RNasel ...

Many other handles exist that are cleavable by orthogonal mechanisms for the synthesis of protected peptide fragments these are also summarized in Table 5. A novel strategy for the synthesis of cyclic peptides on resin is to attach the peptide to the resin by a backbone nitrogen rather that the C -carboxyl. The N-and C-termini then remain free for further functionalization such as cyclization, esterification, or thioester formation. This backbone amide linker (BAL) is listed in Table 5. Other strategies such as attaching the peptide to the resin via the side chain of trifunctional amino acids and more comprehensive listings of linkers and handles are covered in References 9,12, and 109-111. 

Same as above/suitable for the synthesis of protected peptide fragments having free carboxyl group 50% TFA... 

Mars 1970 Marshall, D.L. and Liener, I.E., A Modified Support for Solid-Phase Peptide Synthesis Which Permits the Synthesis of Protected Peptide Fragments, J. Org. Chem., 35 (1970) 867-878. 

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