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

被引：288

作者：

Biron, Eric ^{[1
]}

Chatterjee, Jayanta ^{[1
]}

Ovadia, Oded ^{[2
]}

Langenegger, Daniel ^{[3
]}

Brueggen, Joseph

Hoyer, Daniel ^{[3
]}

Schmid, Herbert A. ^{[3
]}

Jelinek, Raz ^{[4
]}

Gilon, Chaim ^{[2
]}

Hoffman, Amnon ^{[2
]}

Kessler, Horst ^{[1
]}

机构：

[1] Tech Univ Munich, Dept Chem, CIPS, D-85747 Garching, Germany

[2] Hebrew Univ Jerusalem, Dept Pharmaceut & Organ Chem, Jerusalem, Israel

[3] Novartis Inst Biomed Res, Basel, Switzerland

[4] Ben Gurion Univ Negev, Dept Chem, Beer Sheva, Israel

来源：

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION | 2008年 / 47卷 / 14期

关键词：

bioavailability; cyclic peptides; N methylation; peptide drugs; somatostatin;

D O I：

10.1002/anie.200705797

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

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) © 2008 Wiley-VCH Verlag GmbH & Co. KGaA.

引用

页码：2595 / 2599

页数：5