Protecting groups, deprotection solid phase peptide synthesis

The 9-fluorenylmethoxycarbonyl group, developed by Carpino and co-workers in 1972 [257], has become one of the most widely used protective groups for aliphatic or aromatic amines in solid-phase synthesis. For solid-phase peptide synthesis in particular, this protective group plays an important role [258] (Section 16.1). The Fmoc group is not well suited for liquid-phase synthesis because non-volatile side products are formed during deprotection. 

All peptides were prepared by solid-phase peptide synthesis on a peptide synthesizer. [1171 Various protection groups were used for the terminal positions and side-chain functionalities of the amino acids. The coupling mixture consisted of HBTU/HOBt/amino acid/NMM. Deprotection of the desired side chains with piperidine in NMP, followed by cyclization with HBTU/HOBt/NMM in HFIP/NMP, led to the formation of lactam bridges on the resin. 

Solid-phase peptide synthesis is based on the sequential addition of protected amino acids onto an insoluble support. Addition proceeds from carboxy terminus to amino terminus. The first amino acid is attached to a solid support by a linker and, if necessary, side-chain amino acid function is protected throughout chain assembly. The carboxy group of the in-coming, acylating amino acid is activated for coupling while its amino group is protected temporarily for each coupling step and then deprotected for the next cycle. The... 

In solid phase peptide synthesis, polypeptides are chemically synthesized by addition of free amino acids to a tethered peptide. To prevent unwanted reactions, the a-amino group and reactive side chain groups of the free amino acids are chemically protected or blocked, and then deprotected or deblocked once the amino acid is attached to the growing polypeptide chain. 

Peptide synthesis Polypeptides can be chemically synthesized by covalently linking amino acids to the end of a growing polypeptide chain. In solid phase peptide synthesis the growing polypeptide chain is covalently anchored at its C-terminus to an insoluble support such as polystyrene beads. The next amino acid in the sequence has to react with the free a-amino group on the tethered peptide, but it has a free a-amino group itself which will also react. To overcome this problem the free amino acid has its a-amino group chemically protected (blocked) so that it does not react with other molecules. Once the new amino acid is coupled, its now N-terminal a-amino group is deprotected (deblocked) so that the next... 

The Fmoc group protection is common in solid-phase peptide synthesis. Fmoc is resistant to acidic conditions and easily deprotected by weak bases, particularly secondary amines. Deprotection occurs through base-catalyzed abstraction of the (3-proton of the protecting group with elimination leading to formation of dibenzofulvene (1.83) (Scheme 1.36). 

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