Improving oral bioavailability of peptides by multiple N-methylation: Somatostatin analogues

Eric Biron; Jayanta Chatterjee; Oded Ovadia; Daniel Langenegger; Joseph Brueggen; Daniel Hoyer; Herbert A. Schmid; Raz Jelinek; Chaim Gilon; Amnon Hoffman; Horst Kessler

doi:10.1002/anie.200705797

Improving oral bioavailability of peptides by multiple N-methylation: Somatostatin analogues

Eric Biron^*, Jayanta Chatterjee, Oded Ovadia, Daniel Langenegger, Joseph Brueggen, Daniel Hoyer, Herbert A. Schmid, Raz Jelinek, Chaim Gilon, Amnon Hoffman, Horst Kessler

^*Corresponding author for this work

School of Pharmacy

Research output: Contribution to journal › Article › peer-review

309 Scopus citations

Abstract

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-methylationis allowed at specific positions without affecting the bioactive conformation. (Figure Presented)

Original language	English
Pages (from-to)	2595-2599
Number of pages	5
Journal	Angewandte Chemie - International Edition
Volume	47
Issue number	14
DOIs	https://doi.org/10.1002/anie.200705797
State	Published - 25 Mar 2008

Keywords

Bioavailability
Cyclic peptides
N methylation
Peptide drugs
Somatostatin

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10.1002/anie.200705797

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abstract = "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-methylationis allowed at specific positions without affecting the bioactive conformation. (Figure Presented)",

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AU - Ovadia, Oded

AU - Langenegger, Daniel

AU - Brueggen, Joseph

AU - Hoyer, Daniel

AU - Schmid, Herbert A.

AU - Jelinek, Raz

AU - Gilon, Chaim

AU - Hoffman, Amnon

AU - Kessler, Horst

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KW - Cyclic peptides

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Improving oral bioavailability of peptides by multiple N-methylation: Somatostatin analogues

Abstract

Keywords

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