Journal
ACS CHEMICAL BIOLOGY
Volume 13, Issue 8, Pages 2003-2009Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acschembio.8b00488
Keywords
-
Categories
Funding
- JC Bose Fellowship
- DST, Govt. of India
- CSIR
- DBT [BT/PR13023/MED/31/311/2015]
- Ramalingaswami Fellowship
- UGC
Ask authors/readers for more resources
DNA, as a target for therapeutic intervention, remains largely unexplored. DLX-4, a homeodomain containing transcription factor, and its spliced isoforms play crucial roles in many aspects of cellular biochemistry and important roles in many diseases. A smaller peptide mimicking the homeodomain of the transcription factor DLX-4 was designed and synthesized by suitable conjoining of its modified DNA-binding elements. The peptide binds to DLX-4 target sites on the regulatory region of the globin gene cluster with native-like affinity and specificity in vitro. When conjugated to cell penetrating and nuclear localization sequences, it upregulated some of the genes repressed by DLX-4 or its isoforms, such as beta- and gamma-globin genes in erythropoietin-induced differentiating CD34(+) human hematopoietic stem/progenitor cells with high specificity by competing with the respective binding sites. Engineered peptides mimicking DNA-binding domains of transcription factors offer the potential for creating synthetic molecules for directly targeting DNA sites with high specificity.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available