Enzyme-labile protecting groups

For peptide synthesis, enzyme-labile protecting groups are particularly useful for the construction and manipulation of larger peptide units, i.e. for transformations which, for solu-bihty reasons, have to be carried out in aqueous systems. There are also applications for this technique in the reprocessing of peptides obtained by recombinant DNA technology. 

An application of the concept of combining enzyme-labile protecting groups with chemically labile ones is illustrated by the chemoenzymatic synthesis of the S-palmitoylated and S-farnesylated C-terminal lipohexapeptide of the human N-Ras protein (Scheme... 

Figure 1 Selected enzyme-labile protecting groups.

The fhioethyl group present in the anchor group of (40) was activated by treatment with N-iodosuccinimide (NIS) followed by displacement with a variety of alcohols (44-46). To prove the possible application of this linker in solid phase carbohydrate synthesis, protected glycosides (47) and (48) were coupled to linker (40) and released enzymatically. Flitsch et al. also described the immobilization and enzymatic cleavage on a variety of amines [41]. Nevertheless, the application of this enzyme-labile hnker group in multi-step syntheses on the solid phase and subsequent enzyme-initiated release from the polymeric support has not been described yet. 

Enzyme Labile Carboxyl Protecting Groups Choline Ester (OCho)... 

Initial attempts to introduce an enzyme-labile amino protecting group involved the use of chymotrypsin for the removal of AT-benzoylphenylalanine (Bz-Phe) from the tripeptide Bz-Phe-Leu-Leu-OHt l to generate H-Leu-Leu-OH. However, chymotrypsin is an endo-peptidase of rather broad substrate tolerance, catalyzing the hydrolysis of peptide bonds on the carboxy group of hydrophobic and aromatic amino acid residues. Since such amino adds appear widely in peptides and no method is available to protect them against attack by the enzyme during the attempted deprotection, the use of chymotrypsin is problematic its uses are limited to special cases. 

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