Somatropin is a recombinant human growth hormone, consisting of 191 amino acids. This protein is clinically used in children and adults with inadequate endogenous growth hormone to stimulate a normal bone and muscle growth.
In addition, somatropin is currently being investigated for the diagnosis and radiotherapy of certain hormonal cancers. The modification of the protein with the chelating agent NOTA (1,4,7-triazacyclononane-1,4,7-triacetic acid) allows the inclusion of metals coupled to the protein for diagnostic (e.g. 68Ga) or therapeutic (e.g. 90Y) purposes. The NOTA unit is selectively introduced on a lysine side chain. This yields 9 possible labelling sites for somatropin:
FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF
We have applied an enzymatic digestion procedure for the characterisation of the modified somatropin, using trypsin, chymotrypsin and Staphylococcus aureus V-8 proteases. The resulting peptides were then monitored using HPLC-MS2, allowing the characterisation of the modified protein
