글로벌 연구동향

분자영상 및 방사화학

본문글자크기
  • 2016년 06월호
    [Angew Chem Int Ed Engl. ] Probing the Small-Molecule Inhibition of an Anticancer Therapeutic Protein-Protein Interaction Using a Solid-State Nanopore.

    서울대, 한국생명공학연구원/곽동규, 김기범*, 지성욱*

  • 출처
    Angew Chem Int Ed Engl.
  • 등재일
    2016 May 4
  • 저널이슈번호
    55(19):5713-7. doi: 10.1002/anie.201511601.
  • 내용

    바로가기  >

    Abstract

    Nanopore sensing is an emerging technology for the single-molecule-based detection of various biomolecules. In this study, we probed the anticancer therapeutic p53 transactivation domain (p53TAD)/MDM2 interaction and its inhibition with a small-molecule MDM2 antagonist, Nutlin-3, using low-noise solid-state nanopores. Although the translocation of positively charged MDM2 through a nanopore was detected at the applied negative voltage, this MDM2 translocation was almost completely blocked upon formation of the MDM2/GST-p53TAD complex owing to charge conversion. In combination with NMR data, the nanopore measurements showed that the addition of Nutlin-3 rescued MDM2 translocation, indicating that Nutlin-3 disrupted the MDM2/GST-p53TAD complex, thereby releasing MDM2. Taken together, our results reveal that solid-state nanopores can be a valuable platform for the ultrasensitive, picomole-scale screening of small-molecule drugs against protein-protein interaction (PPI) targets. 

     

    Author information

    Kwak DK1,2, Chae H3, Lee MK1, Ha JH1, Goyal G4, Kim MJ4,5, Kim KB6, Chi SW7,8.​

    1Structural Biology & Nanopore Research Laboratory, Disease Target Structure Research Center, KRIBB, 125 Gwahak-ro, Yuseong-gu, Daejeon, 34141, Republic of Korea.

    2Department of Bio-Analytical Sciences, Korea University of Science and Technology, 217 Gajeong-ro, Yuseong-gu, Daejeon, 34113, Republic of Korea.

    3Department of Materials Science and Engineering, Seoul National University, 599 Gwanak-ro, Gwanak-gu, Seoul, 08826, Republic of Korea.

    4School of Biomedical Engineering, Science and Health Systems Drexel University, 3701 Market Street, Philadelphia, PA, 19104, USA.

    5Department of Mechanical Engineering and Mechanics, Drexel University, 3701 Market Street, Philadelphia, PA, 19104, USA.

    6Department of Materials Science and Engineering, Seoul National University, 599 Gwanak-ro, Gwanak-gu, Seoul, 08826, Republic of Korea. kibum@snu.ac.kr.

    7Structural Biology & Nanopore Research Laboratory, Disease Target Structure Research Center, KRIBB, 125 Gwahak-ro, Yuseong-gu, Daejeon, 34141, Republic of Korea. swchi@kribb.re.kr.

    8Department of Bio-Analytical Sciences, Korea University of Science and Technology, 217 Gajeong-ro, Yuseong-gu, Daejeon, 34113, Republic of Korea. swchi@kribb.re.kr. 

  • 키워드
    MDM2; drug screening; p53; protein-protein interactions; solid-state nanopores

  • 편집위원

    Nanopore sensing 기법은 다양한 biomolecule의 detection을 위해 폭넓게 사용되는 기법이다. 이번 연구에서는 MADM2 antagonist인 Nutlin-3가 항암치료의 표적인 p53TAD/MDM2의 interaction을 저해함을 가시화했음.

    덧글달기2016-06-02 10:38:36

  • 편집위원

    NMR 결과와의 종합분석을 통해, Nutlin-3가 MDM2/GST-p53TAD의 complex 형성을 저해함으로써, MDM2의 release에 관여함으로 증명하였음.

    2016-06-02 10:38:36

  • 편집위원

    본 연구는 solid-state nanopores가 small-molecule drug의 screening과정에 효과적으로 사용될 수 있음을 제시한 결과입니다.

    2016-06-02 10:38:36

  • 덧글달기
    덧글달기
       IP : 3.143.228.40

    등록

목록