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Proteome-wide covalent ligand discovery in native biological systems

Author

Listed:
  • Keriann M. Backus

    (The Scripps Research Institute. La Jolla)

  • Bruno E. Correia

    (The Scripps Research Institute. La Jolla)

  • Kenneth M. Lum

    (The Scripps Research Institute. La Jolla)

  • Stefano Forli

    (The Scripps Research Institute. La Jolla)

  • Benjamin D. Horning

    (The Scripps Research Institute. La Jolla)

  • Gonzalo E. González-Páez

    (The Scripps Research Institute. La Jolla)

  • Sandip Chatterjee

    (The Scripps Research Institute. La Jolla)

  • Bryan R. Lanning

    (The Scripps Research Institute. La Jolla)

  • John R. Teijaro

    (The Scripps Research Institute. La Jolla)

  • Arthur J. Olson

    (The Scripps Research Institute. La Jolla)

  • Dennis W. Wolan

    (The Scripps Research Institute. La Jolla)

  • Benjamin F. Cravatt

    (The Scripps Research Institute. La Jolla)

Abstract

Small molecules are powerful tools for investigating protein function, and can serve as leads for new therapeutics, but most human proteins lack known small-molecule ligands; here, a quantitative analysis of cysteine-reactive small-molecule fragments screened against thousands of proteins is reported.

Suggested Citation

  • Keriann M. Backus & Bruno E. Correia & Kenneth M. Lum & Stefano Forli & Benjamin D. Horning & Gonzalo E. González-Páez & Sandip Chatterjee & Bryan R. Lanning & John R. Teijaro & Arthur J. Olson & Denn, 2016. "Proteome-wide covalent ligand discovery in native biological systems," Nature, Nature, vol. 534(7608), pages 570-574, June.
  • Handle: RePEc:nat:nature:v:534:y:2016:i:7608:d:10.1038_nature18002
    DOI: 10.1038/nature18002
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    Cited by:

    1. Wai Cheung Chan & Xiaoxi Liu & Robert S. Magin & Nicholas M. Girardi & Scott B. Ficarro & Wanyi Hu & Maria I. Tarazona Guzman & Cara A. Starnbach & Alejandra Felix & Guillaume Adelmant & Anthony C. Va, 2023. "Accelerating inhibitor discovery for deubiquitinating enzymes," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    2. Ádám Levente Póti & Dániel Bálint & Anita Alexa & Péter Sok & Kristóf Ozsváth & Krisztián Albert & Gábor Turczel & Sarolt Magyari & Orsolya Ember & Kinga Papp & Sándor Balázs Király & Tímea Imre & Kri, 2024. "Targeting a key protein-protein interaction surface on mitogen-activated protein kinases by a precision-guided warhead scaffold," Nature Communications, Nature, vol. 15(1), pages 1-22, December.
    3. Andrew J. Heindel & Jeffrey W. Brulet & Xiantao Wang & Michael W. Founds & Adam H. Libby & Dina L. Bai & Michael C. Lemke & David M. Leace & Thurl E. Harris & Markus Hafner & Ku-Lung Hsu, 2023. "Chemoproteomic capture of RNA binding activity in living cells," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    4. Chenlu Zhang & Chen Zhou & Assa Magassa & Xiaokang Jin & Deyu Fang & Xiaoyu Zhang, 2024. "A platform for mapping reactive cysteines within the immunopeptidome," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    5. Heta Desai & Katrina H. Andrews & Kristina V. Bergersen & Samuel Ofori & Fengchao Yu & Flowreen Shikwana & Mark A. Arbing & Lisa M. Boatner & Miranda Villanueva & Nicholas Ung & Elaine F. Reed & Alexe, 2024. "Chemoproteogenomic stratification of the missense variant cysteinome," Nature Communications, Nature, vol. 15(1), pages 1-24, December.
    6. Anna Rodina & Chao Xu & Chander S. Digwal & Suhasini Joshi & Yogita Patel & Anand R. Santhaseela & Sadik Bay & Swathi Merugu & Aftab Alam & Pengrong Yan & Chenghua Yang & Tanaya Roychowdhury & Palak P, 2023. "Systems-level analyses of protein-protein interaction network dysfunctions via epichaperomics identify cancer-specific mechanisms of stress adaptation," Nature Communications, Nature, vol. 14(1), pages 1-26, December.
    7. Jing Gao & Bo Hou & Qiwen Zhu & Lei Yang & Xingyu Jiang & Zhifeng Zou & Xutong Li & Tianfeng Xu & Mingyue Zheng & Yi-Hung Chen & Zhiai Xu & Huixiong Xu & Haijun Yu, 2022. "Engineered bioorthogonal POLY-PROTAC nanoparticles for tumour-specific protein degradation and precise cancer therapy," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    8. Tin-Yan Koo & Hinyuk Lai & Daniel K. Nomura & Clive Yik-Sham Chung, 2023. "N-Acryloylindole-alkyne (NAIA) enables imaging and profiling new ligandable cysteines and oxidized thiols by chemoproteomics," Nature Communications, Nature, vol. 14(1), pages 1-19, December.

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