Proximity-enabled bioreactivity to generate covalent peptide inhibitors of p53-Mdm4

被引：69

作者：

Hoppmann, Christian

Wang, Lei ^{[1
]}

机构：

[1] Univ Calif San Francisco, Dept Pharmaceut Chem, 555 Mission Bay Blvd South, San Francisco, CA 94158 USA

来源：

CHEMICAL COMMUNICATIONS | 2016年 / 52卷 / 29期

关键词：

SULFONYL FLUORIDES; STAPLED PEPTIDES; P53; PROTEINS; BINDING; CELLS; MDM2;

D O I：

10.1039/c6cc01226d

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Although small molecule covalent inhibitors have been widely explored, macromolecular covalent inhibitors are more difficult to design and implement. Here we present a strategy to enable a peptide to bind to its target protein covalently via proximity-enabled bio-reactivity, improving its activity of inhibiting the p53-Mdm4 interaction by 10-fold.

引用

页码：5140 / 5143

页数：4

共 27 条

[1] Structure of the Stapled p53 Peptide Bound to Mdm2 [J].

Baek, Sohee ;

Kutchukian, Peter S. ;

Verdine, Gregory L. ;

Huber, Robert ;

Holak, Tad A. ;

Lee, Ki Won ;

Popowicz, Grzegorz M. .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2012, 134 (01) :103-106

[2] Reactivation of the p53 tumor suppressor pathway by a stapled p53 peptide [J].

Bernal, Federico ;

Tyler, Andrew F. ;

Korsmeyer, Stanley J. ;

Walensky, Loren D. ;

Verdine, Gregory L. .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2007, 129 (09) :2456-+

[3] A Stapled p53 Helix Overcomes HDMX-Mediated Suppression of p53 [J].

Bernal, Federico ;

Wade, Mark ;

Godes, Marina ;

Davis, Tina N. ;

Whitehead, David G. ;

Kung, Andrew L. ;

Wahl, Geoffrey M. ;

Walensky, Loren D. .

CANCER CELL, 2010, 18 (05) :411-422

[4] Photoreactive Stapled BH3 Peptides to Dissect the BCL-2 Family Interactome [J].

Braun, Craig R. ;

Mintseris, Julian ;

Gavathiotis, Evripidis ;

Bird, Gregory H. ;

Gygi, Steven P. ;

Walensky, Loren D. .

CHEMISTRY & BIOLOGY, 2010, 17 (12) :1325-1333

[5] Peptido Sulfonyl Fluorides as New Powerful Proteasome Inhibitors [J].

Brouwer, Arwin J. ;

Jonker, Anika ;

Werkhoven, Paul ;

Kuo, Ethan ;

Li, Nan ;

Gallastegui, Nerea ;

Kernmink, Johan ;

Florea, Bogdan I. ;

Groll, Michael ;

Overkleeft, Herman S. ;

Liskamp, Rob M. J. .

JOURNAL OF MEDICINAL CHEMISTRY, 2012, 55 (24) :10995-11003

[6] Stapled Peptides with Improved Potency and Specificity That Activate p53 [J].

Brown, Christopher J. ;

Quah, Soo T. ;

Jong, Janice ;

Goh, Amanda M. ;

Chiam, Poh C. ;

Khoo, Kian H. ;

Choong, Meng L. ;

Lee, May A. ;

Yurlova, Larisa ;

Zolghadr, Kourosh ;

Joseph, Thomas L. ;

Verma, Chandra S. ;

Lane, David P. .

ACS CHEMICAL BIOLOGY, 2013, 8 (03) :506-512

[7] Awakening guardian angels: drugging the p53 pathway [J].

Brown, Christopher J. ;

Lain, Sonia ;

Verma, Chandra S. ;

Fersht, Alan R. ;

Lane, David P. .

NATURE REVIEWS CANCER, 2009, 9 (12) :862-873

[8] Stapled α-helical peptide drug development: A potent dual inhibitor of MDM2 and MDMX for p53-dependent cancer therapy [J].

Chang, Yong S. ;

Graves, Bradford ;

Guerlavais, Vincent ;

Tovar, Christian ;

Packman, Kathryn ;

To, Kwong-Him ;

Olson, Karen A. ;

Kesavan, Kamala ;

Gangurde, Pranoti ;

Mukherjee, Aditi ;

Baker, Theresa ;

Darlak, Krzysztof ;

Elkin, Carl ;

Filipovic, Zoran ;

Qureshi, Farooq Z. ;

Cai, Hongliang ;

Berry, Pamela ;

Feyfant, Eric ;

Shi, Xiangguo E. ;

Horstick, James ;

Annis, D. Allen ;

Manning, Anthony M. ;

Fotouhi, Nader ;

Nash, Huw ;

Vassilev, Lyubomir T. ;

Sawyer, Tomi K. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2013, 110 (36) :E3445-E3454

[9] Genetically Encoding an Electrophilic Amino Acid for Protein Stapling and Covalent Binding to Native Receptors [J].

Chen, Xiao-Hua ;

Xiang, Zheng ;

Hu, Ying S. ;

Lacey, Vanessa K. ;

Cang, Hu ;

Wang, Lei .

ACS CHEMICAL BIOLOGY, 2014, 9 (09) :1956-1961

[10] Towards understanding cell penetration by stapled peptides [J].

Chu, Qian ;

Moellering, Raymond E. ;

Hilinski, Gerard J. ;

Kim, Young-Woo ;

Grossmann, Tom N. ;

Yeh, Johannes T. -H. ;

Verdine, Gregory L. .

MEDCHEMCOMM, 2015, 6 (01) :111-119

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