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

共 13 条

[1] Improving oral bioavailability of cyclic peptides by N-methylation
Raeder, Andreas F. B.
Reichart, Florian
Weinmueller, Michael
Kessler, Horst
BIOORGANIC & MEDICINAL CHEMISTRY, 2018, 26 (10) : 2766 - 2773
[2] N-Methylation of Peptides and Proteins: An Important Element for Modulating Biological Functions
Chatterjee, Jayanta
Rechenmacher, Florian
Kessler, Horst
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2013, 52 (01) : 254 - 269
[3] N-methylation in amino acids and peptides: Scope and limitations
Sharma, Anamika
Kumar, Ashish
Monaim, Shimaa A. H. Abdel
Jad, Yahya E.
El-Faham, Ayman
de la Torre, Beatriz G.
Albericio, Fernando
BIOPOLYMERS, 2018, 109 (10)
[4] Optimized selective N-methylation of peptides on solid support
Biron, E
Chatterjee, J
Kessler, H
JOURNAL OF PEPTIDE SCIENCE, 2006, 12 (03) : 213 - 219
[5] The Effect of Multiple N-Methylation on Intestinal Permeability of Cyclic Hexapeptides
Ovadia, Oded
Greenberg, Sarit
Chatterjee, Jayanta
Laufer, Burkhardt
Opperer, Florian
Kessler, Horst
Gilon, Chaim
Hoffman, Amnon
MOLECULAR PHARMACEUTICS, 2011, 8 (02) : 479 - 487
[6] Backbone N-methylation of peptides: Advances in synthesis and applications in pharmaceutical drug development
Li, Xuefei
Wang, Ningchao
Liu, Yuhang
Li, Weipiao
Bai, Xinyu
Liu, Ping
He, Chun -Yang
BIOORGANIC CHEMISTRY, 2023, 141
[7] On-resin N-methylation of cyclic peptides for discovery of orally bioavailable scaffolds
White, Tina R.
Renzelman, Chad M.
Rand, Arthur C.
Rezai, Taha
McEwen, Cayla M.
Gelev, Vladimir M.
Turner, Rushia A.
Linington, Roger G.
Leung, Siegfried S. F.
Kalgutkar, Amit S.
Bauman, Jonathan N.
Zhang, Yizhong
Liras, Spiros
Price, David A.
Mathiowetz, Alan M.
Jacobson, Matthew P.
Lokey, R. Scott
NATURE CHEMICAL BIOLOGY, 2011, 7 (11) : 810 - 817
[8] Converting polar cyclic peptides into membrane permeable molecules using N-methylation
Lee, Leo L. H.
Buckton, Laura K.
McAlpine, Shelli R.
PEPTIDE SCIENCE, 2018, 110 (03):
[9] N terminal N-methylation modulates chiral centre induced helical (CIH) peptides' biophysical properties
Li, Wenjun
Hu, Kuan
Zhang, Qingzhou
Wang, Dongyuan
Ma, Yue
Hou, Zhanfeng
Yin, Feng
Li, Zigang
CHEMICAL COMMUNICATIONS, 2018, 54 (15) : 1865 - 1868
[10] Structure-activity relationship and metabolic stability studies of backbone cyclization and N-methylation of melanocortin peptides
Linde, Yaniv
Ovadia, Oded
Safrai, Eli
Xiang, Zhimin
Portillo, Federico P.
Shalev, Deborah E.
Haskell-Luevano, Carrie
Hoffman, Amnon
Gilon, Chaim
BIOPOLYMERS, 2008, 90 (05) : 671 - 682

← 1 2 →