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
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