Selective alkylation and acylation of alpha and epsilon amino groups with PEG in a somatostatin analogue: tailored chemistry for optimized bioconjugates.

The effects of the type and location of polymer grafting on the biological activity of different mono-PEG derivatives of the somatostatin analogue RC160 were evaluated. A chemical strategy to obtain mono-PEG alkylation or acylation of the peptide's alpha-terminal or lysil-epsilon primary amines was devised. Selective BOC protection of the two available primary amines, followed by reaction with two different PEG reagents and removal of the protecting group, was carried out.