Selective and Potent Proteomimetic Inhibitors of Intracellular Protein-Protein Interactions

被引：72

作者：

Barnard, Anna ^{[1
,2
]}

Long, Kerya ^{[1
,2
]}

Martin, Heather L. ^{[3
]}

Miles, Jennifer A. ^{[1
,2
]}

Edwards, Thomas A. ^{[2
,4
]}

Tomlinson, Darren C. ^{[2
,4
]}

Macdonald, Andrew ^{[2
,4
]}

Wilson, Andrew J. ^{[1
,2
]}

机构：

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

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

[3] Univ Leeds, St Jamess Univ Hosp, Leeds Inst Biomed & Clin Sci, Leeds LS9 7TF, W Yorkshire, England

[4] Univ Leeds, Sch Mol & Cellular Biol, Leeds LS2 9JT, W Yorkshire, England

来源：

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION | 2015年 / 54卷 / 10期

基金：

英国工程与自然科学研究理事会; 英国惠康基金; 欧洲研究理事会;

关键词：

apoptosis; foldamers; helical structures; peptidomimetics; protein-protein interactions; ALPHA-HELIX MIMETICS; MDM2; INHIBITOR; P53; ACTIVATION; AUTOPHAGY; APOPTOSIS; PEPTIDE; CANCER; MCL-1; ANTAGONISTS;

D O I：

10.1002/anie.201410810

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Inhibition of protein-protein interactions (PPIs) represents a major challenge in chemical biology and drug discovery. -Helix mediated PPIs may be amenable to modulation using generic chemotypes, termed proteomimetics, which can be assembled in a modular manner to reproduce the vectoral presentation of key side chains found on a helical motif from one partner within the PPI. In this work, it is demonstrated that by using a library of N-alkylated aromatic oligoamide helix mimetics, potent helix mimetics which reproduce their biophysical binding selectivity in a cellular context can be identified.

引用

页码：2960 / 2965

页数：6

共 52 条

[1]

Azzarito V, 2013, NAT CHEM, V5, P161, DOI [10.1038/nchem.1568, 10.1038/NCHEM.1568]

[2] Orthogonal functionalisation of α-helix mimetics [J].

Barnard, Anna ;

Long, Kerya ;

Yeo, David J. ;

Miles, Jennifer A. ;

Azzarito, Valeria ;

Burslem, George M. ;

Prabhakaran, Panchami ;

Edwards, Thomas A. ;

Wilson, Andrew J. .

ORGANIC & BIOMOLECULAR CHEMISTRY, 2014, 12 (35) :6794-6799

[3] Autophagy: assays and artifacts [J].

Barth, Sandra ;

Glick, Danielle ;

Macleod, Kay F. .

JOURNAL OF PATHOLOGY, 2010, 221 (02) :117-124

[4] Modulation of protein-protein interactions with small organic molecules [J].

Berg, T .

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2003, 42 (22) :2462-2481

[5] Unravelling mechanisms of p53-mediated tumour suppression [J].

Bieging, Kathryn T. ;

Mello, Stephano Spano ;

Attardi, Laura D. .

NATURE REVIEWS CANCER, 2014, 14 (05) :359-370

[6] The apoptotic pore on mitochondria: are we breaking through or still stuck? [J].

Borner, C. ;

Andrews, D. W. .

CELL DEATH AND DIFFERENTIATION, 2014, 21 (02) :187-191

[7] Studies leading to potent, dual inhibitors of bcl-2 and Bcl-xL [J].

Bruncko, Milan ;

Oost, Thorsten K. ;

Belli, Barbara A. ;

Ding, Hong ;

Joseph, Mary K. ;

Kunzer, Aaron ;

Martineau, Darlene ;

McClellan, William J. ;

Mitten, Michael ;

ng, Shi-Chu Ng ;

Nimmer, Paul M. ;

Oltersdorf, Tilman ;

Park, Cheol-Min ;

Petros, Andrew M. ;

Shoemaker, Alexander R. ;

Song, Xiaohong ;

Wang, Xilu ;

Wendt, Michael D. ;

Zhang, Haichao ;

Fesik, Stephen W. ;

Rosenberg, Saul H. ;

Elmore, Steven W. .

JOURNAL OF MEDICINAL CHEMISTRY, 2007, 50 (04) :641-662

[8] Assessing Helical Protein Interfaces for Inhibitor Design [J].

Bullock, Brooke N. ;

Jochim, Andrea L. ;

Arora, Paramjit S. .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2011, 133 (36) :14220-14223

[9] Small-Molecule Proteomimetic Inhibitors of the HIF-1α-p300 Protein-Protein Interaction [J].

Burslem, George M. ;

Kyle, Hannah F. ;

Breeze, Alexander L. ;

Edwards, Thomas A. ;

Nelson, Adam ;

Warriner, Stuart L. ;

Wilson, Andrew J. .

CHEMBIOCHEM, 2014, 15 (08) :1083-1087

[10] Isolation, Identification and Activities of Natural Antioxidants from Callicarpa kwangtungensis Chun [J].

Cai, Hao ;

Xie, Zhiyong ;

Liu, Guanghui ;

Sun, Xiuman ;

Peng, Guangtian ;

Lin, Baoqin ;

Liao, Qiongfeng .

PLOS ONE, 2014, 9 (03)

← 1 2 3 4 5 6 →