Combined Approach of Backbone Amide Linking and On-Resin N-Methylation for the Synthesis of Bioactive and Metabolically Stable Peptides

被引：5

作者：

Wesche, Frank ^{[1
]}

Adihou, Helene ^{[1
]}

Kaiser, Astrid ^{[2
]}

Wurglics, Mario ^{[2
]}

Schubert-Zsilavecz, Manfred ^{[2
]}

Kaiser, Marcel ^{[3
,4
]}

Bode, Helge B. ^{[1
,5
]}

机构：

[1] Goethe Univ Frankfurt, Fachbereich Biowissensch, Mol Biotechnol, Max von Laue Str 9, D-60438 Frankfurt, Germany

[2] Goethe Univ Frankfurt, Inst Pharmaceut Chem, Max von Laue Str 9, D-60438 Frankfurt, Germany

[3] Swiss Trop & Publ Hlth Inst, Parasite Chemotherapy, Socinstr 57, CH-4051 Basel, Switzerland

[4] Univ Basel, Peterspl 1, CH-4003 Basel, Switzerland

[5] Goethe Univ Frankfurt, Buchmann Inst Mol Life Sci BMLS, Max von Laue Str 15, D-60438 Frankfurt, Germany

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2018年 / 61卷 / 09期

关键词：

NATURAL-PRODUCTS; ENTOMOPATHOGENIC BACTERIA; COMBINATORIAL LIBRARIES; ARTIFICIAL MEMBRANES; DIMETHYL-SULFOXIDE; ALANINE SCAN; AMINO-ACIDS; IN-SITU; PHASE; PERMEABILITY;

D O I：

10.1021/acs.jmedchem.7b01809

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Rhabdopeptides are a large class of nonribosomal peptides from the bacteria Xenorhabdus and Photorhabdus with low micromolar activity against different protozoa, which are the causative agents of several tropical diseases. The development of a facile and flexible synthesis combining backbone amide linking with on-resin peralkylation for the synthesis of permethylated rhabdopeptides is described. This strategy allows the fast generation of permethylated naturally occurring and artificial rhabdopeptides for a structure activity study. Furthermore, in vitro experiments revealed their superior properties regarding their stability and passive membrane diffusion.

引用

页码：3930 / 3938

页数：9

共 3 条

[1] SYNTHESIS OF NATURAL AND NON-NATURAL RHABDOPEPTIDES VIA ON-RESIN N-METHYLATION AND BACKBONE AMID LINKING
Wesche, F.
Adihou, H.
Bode, H. B.
JOURNAL OF PEPTIDE SCIENCE, 2016, 22 : S76 - S76
[2] 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
[3] Amide-to-ester substitution as a stable alternative to N-methylation for increasing membrane permeability in cyclic peptides
Hosono, Yuki
Uchida, Satoshi
Shinkai, Moe
Townsend, Chad E.
Kelly, Colin N.
Naylor, Matthew R.
Lee, Hsiau-Wei
Kanamitsu, Kayoko
Ishii, Mayumi
Ueki, Ryosuke
Ueda, Takumi
Takeuchi, Koh
Sugita, Masatake
Akiyama, Yutaka
Lokey, Scott R.
Morimoto, Jumpei
Sando, Shinsuke
NATURE COMMUNICATIONS, 2023, 14 (01)

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