Improving oral bioavailability of peptides by multiple N-methylation: Somatostatin analogues Academic Article uri icon


  • Low bioavailability of peptides following oral administration is attributed to their inactivation in the gastro–intestinal tract through enhanced enzymatic degradation in the gut wall by a variety of peptidases expressed at the enterocytes brush border,[1] and to poor intestinal permeation.[2] In addition, the instability of peptides toward peptidases in the systemic blood circulation causes rapid elimination (ie, short half-life). These factors limit the use of peptides as therapeutic agents in the clinical setting. Several strategies have been used to reduce enzymatic cleavage and uptake into the systemic blood circulation, including prodrug approaches, peptidomimetics, and structural modifications, such as covalent attachment of polyethylene glycol (PEG),[3] lipidation,[4] and chemical modifications, for example, cyclization,[5] d-amino acid substitution, and N-methylation.[6] Cyclic peptides show …

publication date

  • January 1, 2008