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

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

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...

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Veröffentlicht in:Angewandte Chemie (International ed.) 2008-03, Vol.47 (14), p.2595-2599
Hauptverfasser: Biron, Eric, Chatterjee, Jayanta, Ovadia, Oded, Langenegger, Daniel, Brueggen, Joseph, Hoyer, Daniel, Schmid, Herbert A, Jelinek, Raz, Gilon, Chaim, Hoffman, Amnon, Kessler, Horst
Format: Artikel
Sprache:eng
Schlagworte:
Administration, Oral
Animals
bioavailability
Biological Availability
Caco-2 Cells
cyclic peptides
Humans
Methylation
Models, Molecular
Molecular Structure
N methylation
peptide drugs
Rats
somatostatin
Somatostatin - administration & dosage
Somatostatin - analogs & derivatives
Somatostatin - chemistry
Somatostatin - pharmacokinetics
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Zusammenfassung: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.
ISSN:1433-7851
1521-3773
DOI:10.1002/anie.200705797