Side-chain protecting groups common

Peptide Synthesis and Self-Assembly Table 1 Common side-chain protecting groups... 

In each step of the usual C-to-N peptide synthesis the N-protecting group of the newly coupled amino acid must be selectively removed under conditions that leave all side-chain protecting groups of the peptide intact. The most common protecting groups of side-chains (p. 229) are all stable towards 50% trifluoroacetic acid in dichloromethane, and this reagent is most commonly used for N"-deprotection. Only /erf-butyl esters and carbamates (=Boc) are solvolyzed in this mixture. 

Table 4. Common side-chain protecting groups used in Fmoc/(6u solid phase peptide synthesis... 

Fig. 2. Commonly used protection scheme based on graduated acidolysis. Temporary JV -amino protection is provided by the tert-butyloxycarbonyl (Boc) group, removed at each step by the moderately strong trifluoroacetic acid (TFA). Permanent benyzl- and cyclohexyl-based side-chain-protecting groups and the phenylacetamidomethyl (PAM) ester handle linkage are cleaved simultaneously at the end of the synthesis by HF to yield the free peptide acid.

Fig. 4 Some common side-chain protecting groups used in Fmoc-SPPS. The relevant amino acids are mentioned beiow. The protecting groups in the left column can be removed with concentrated TFA, while the protecting groups in the right column are stabie to TFA and are removed by other conditions...

On the other hand, if the phosphopeptides are intended to be used in solution-phase assays, the synthesis can be carried out on a standard resin with common linkers. This includes the Rink amide or Wang-type linkers on polystyrene, TentaGel, or ChemMatrix supports. Upon completion of the peptide chain assembly, the peptides are released from the solid support by treatment with TFA-containing cocktails with concomitant removal of acid-labile side-chain protecting groups. Using these conditions robust protocols for rapid and efficient synthesis of phosphopeptides have been established. 

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