Glutaminyl peptides, cyclization

The symmetrical anhydride is prepared using dicyclohexylcarbodiimide in dichloromethane, the urea and solvent are removed, and the anhydride is dissolved in dimethylformamide and added to the peptide-resin (see Section 2.5). The anhydride is a more selective acylating agent than the 0-acylisourea and, thus, gives cleaner reactions than do carbodiimides, but twice as much amino-acid derivative is required, so the method is wasteful. It avoids the acid-catalyzed cyclization of terminal glutaminyl to the pyroglutamate (see Section 6.16) and is particularly effective for acylating secondary amines (see Section 8.15). 

Pyroglutamyl peptides are synthetically accessible either by side-chain cyclization of related glutaminyl and glutamyl peptides or by direct acylation of suitably protected peptides with Na-protected or unprotected pyroglutamic acid. 

Several proteins and bioactive peptides contain an N-terminal pyroglutamic acid residue produced by cyclization of an N-terminal glutaminyl residue. This assay for glutaminyl cyclase follows the reaction for a model peptide. 

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