| Mass spectrometric identification of pyroglutamic acid in peptides following selective hydrolysis (2007) | |||||||||
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| The formation of a pyroglutamyl residue by enzymatic cyclization of an amino terminus glutamine residue is a common posttranslational modification [1–3]. Several biologically active peptides, most notably the thyrotropinreleasing hormone $(TRH)^1$ and gonadotropin-releasing hormone (GnRH), were among the first examples where the N-terminal modification was characterized. The widespread occurrence of glutaminyl cyclase in both plants and animals has ensured that the number of naturally occurring pyroglutamyl peptides is rapidly growing. A recent report established formation of pyroglutamic acid (Z) from N-terminal glutamic acid in recombinant monoclonal antibodies [4]. An N-terminus pyroglutamic acid residue impedes Edman sequencing, necessitating the use of a specific enzyme, pyroglutamate aminopeptidase, to liberate a peptide with a free amino terminus, which is then amenable to automated sequence analysis [5]. During the course of studies aimed at characterizing the peptide components of Conus venom, we encountered several examples of pyroglutamyl peptides. We describe here the serendipitous finding of mild hydrolysis conditions, which permit opening of the pyroglutamyl ring, without significant cleavage of primary and secondary amide bonds. | |||||||||
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