2. Academic Validation
  3. Chem-map profiles drug binding to chromatin in cells

Chem-map profiles drug binding to chromatin in cells

  • Nat Biotechnol. 2023 Jan 23. doi: 10.1038/s41587-022-01636-0.
Zutao Yu # 1,  Jochen Spiegel # 1,  Larry Melidis 2,  Winnie W I Hui 2,  Xiaoyun Zhang 1,  Antanas Radzevičius 1,  Shankar Balasubramanian 3 4 5
Affiliations

Affiliations

  • 1 Yusuf Hamied Department of Chemistry, University of Cambridge, Cambridge, UK.
  • 2 Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK.
  • 3 Yusuf Hamied Department of Chemistry, University of Cambridge, Cambridge, UK. sb10031@cam.ac.uk.
  • 4 Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK. sb10031@cam.ac.uk.
  • 5 School of Clinical Medicine, University of Cambridge, Cambridge, UK. sb10031@cam.ac.uk.
  • # Contributed equally.
PMID: 36690761 DOI: 10.1038/s41587-022-01636-0
Abstract

Characterizing drug-target engagement is essential to understand how small molecules influence cellular functions. Here we present Chem-map for in situ mapping of small molecules that interact with DNA or chromatin-associated proteins, utilizing small-molecule-directed transposase Tn5 tagmentation. We demonstrate Chem-map for three distinct drug-binding modalities as follows: molecules that target a chromatin protein, a DNA secondary structure or that intercalate in DNA. We map the BET bromodomain protein-binding inhibitor JQ1 and provide interaction maps for DNA G-quadruplex structure-binding molecules PDS and PhenDC3. Moreover, we determine the binding sites of the widely used Anticancer drug doxorubicin in human leukemia cells; using the Chem-map of doxorubicin in cells exposed to the histone deacetylase inhibitor tucidinostat reveals the potential clinical advantages of this combination therapy. In situ mapping with Chem-map of small-molecule interactions with DNA and chromatin proteins provides insights that will enhance understanding of genome and chromatin function and therapeutic interventions.

Figures
Products
我们的 Cookie 政策

我们使用 Cookies 和类似技术以提高网站的性能和提升您的浏览体验，部分功能也使用 Cookies 帮助我们更好地理解您的需求，为您提供相关的服务。 如果您有任何关于我们如何处理您个人信息的疑问，请阅读我们的《隐私声明》。

嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z