Improving Oral Bioavailability of Peptides by Multiple N-Methylation: Somatostatin Analogues


  • We thank Humboldt and German Israel Foundation for support and E.B. thanks Alexander von Humboldt foundation for postdoctoral fellowship.


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Full methyl jacket? A complete library of the N-methylated somatostatin cyclopeptidic analogue Veber–Hirschmann peptide cyclo(-PFwKTF-) has been prepared with the aim of improving its bioavailability. Several analogues from the library were found to bind to the somatostatin receptor in the nanomolar range and one of them shows a significant oral bioavailability of 10 %. Conformational analysis shows that N-methylation is allowed at specific positions without affecting the bioactive conformation.