Improving Oral Bioavailability of Peptides by Multiple N-Methylation: Somatostatin Analogues†
Article first published online: 22 FEB 2008
Copyright © 2008 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Angewandte Chemie International Edition
Volume 47, Issue 14, pages 2595–2599, March 25, 2008
How to Cite
Biron, E., Chatterjee, J., Ovadia, O., Langenegger, D., Brueggen, J., Hoyer, D., Schmid, Herbert A., Jelinek, R., Gilon, C., Hoffman, A. and Kessler, H. (2008), Improving Oral Bioavailability of Peptides by Multiple N-Methylation: Somatostatin Analogues. Angew. Chem. Int. Ed., 47: 2595–2599. doi: 10.1002/anie.200705797
We thank Humboldt and German Israel Foundation for support and E.B. thanks Alexander von Humboldt foundation for postdoctoral fellowship.
- Issue published online: 18 MAR 2008
- Article first published online: 22 FEB 2008
- Manuscript Received: 18 DEC 2007
- German Israel Foundation
- cyclic peptides;
- N methylation;
- peptide drugs;
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.