N-alkylated oligoamide α-helical proteomimetics

被引：64

作者：

Campbell, Frederick ^{[2
]}

Plante, Jeffrey P. ^{[2
]}

Edwards, Thomas A. ^{[1
]}

Warriner, Stuart L. ^{[2
]}

Wilson, Andrew J. ^{[2
]}

机构：

[1] Univ Leeds, Astbury Ctr Struct Mol Biol, Leeds LS2 9JT, W Yorkshire, England

[2] Univ Leeds, Sch Chem, Leeds LS2 9JT, W Yorkshire, England

来源：

ORGANIC & BIOMOLECULAR CHEMISTRY | 2010年 / 8卷 / 10期

基金：

英国工程与自然科学研究理事会; 欧洲研究理事会;

关键词：

PROTEIN-PROTEIN INTERACTIONS; SMALL-MOLECULE INHIBITORS; BCL-X-L; P53-HDM2; INTERACTION; PEPTIDE FOLDAMER; IN-VIVO; MIMETICS; ANTAGONISTS; APOPTOSIS; SCAFFOLD;

D O I：

10.1039/c001164a

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

Generic approaches for the design and synthesis of small molecule inhibitors of protein-protein interactions (PPIs) represent a key objective in modern chemical biology. Within this context, the alpha-helix mediated PPIs have received considerable attention as targets for inhibition using small molecules, foldamers and proteomimetics. This manuscript describes a novel N-alkylated aromatic oligoamide proteomimetic scaffold and its solid-phase synthesis-the first time such an approach has been used for proteomimetics. The utility of these scaffolds as proteomimetics is exemplified through the identification of potent mu M inhibitors of the p53-hDM2 helix mediated PPI-a key oncogenic target.

引用

页码：2344 / 2351

页数：8

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