Footprinting, capillary electrophoresis, molecular modelling and NMR studies have been used to examine the binding of a short polyamide to DNA. This molecule, which contains an isopropyl-substituted thiazole in place of one of the N-methylpyrroles, is selective for the sequence 5'-ACTAGT-3' to which it binds with high affinity. Two molecules bind side-by-side in the minor groove, but their binding is staggered so that the molecule reads six base pairs, unlike the related natural products, which tend to bind to four-base-pair sequences. The result suggests that high affinity and selectivity may be gained without resort to very large molecules, which may be difficult to deliver to the site of action.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.bmcl.2003.11.068 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
HP1 Promotes the Centromeric Localization of ATRX and Protects Cohesion by Interfering Wapl Activity in Mitosis.
Front Biosci (Landmark Ed)
January 2025
The Key Laboratory of Model Animals and Stem Cell Biology in Hunan Province, Hunan Normal University Health Science Center, 410013 Changsha, Hunan, China.
Background: α thalassemia/mental retardation syndrome X-linked (ATRX) serves as a part of the sucrose nonfermenting 2 (SNF2) chromatin-remodeling complex. In interphase, ATRX localizes to pericentromeric heterochromatin, contributing to DNA double-strand break repair, DNA replication, and telomere maintenance. During mitosis, most ATRX proteins are removed from chromosomal arms, leaving a pool near the centromere region in mammalian cells, which is critical for accurate chromosome congression and sister chromatid cohesion protection.
View Article and Find Full Text PDFTwo Cysteines in Raf Kinase Inhibitor Protein Make Differential Contributions to Structural Dynamics In Vitro.
Molecules
January 2025
Cancer Microenvironment Branch, Division of Cancer Biology, Research Institute, National Cancer Center, Goyang-si 10408, Republic of Korea.
As a scaffolding protein, Raf kinase binding protein (RKIP) is involved in a variety of cellular pathways, including the Raf-MEK-ERK-cascade. It acts as a negative regulator by binding to its partners, making it an attractive target in the development of therapeutic strategies for cancer. Despite its structural stability as a monomer, RKIP may form a dimer, resulting in the switching of binding partners.
View Article and Find Full Text PDFAn FGF2-Derived Short Peptide Attenuates Bleomycin-Induced Pulmonary Fibrosis by Inhibiting Collagen Deposition and Epithelial-Mesenchymal Transition via the FGFR/MAPK Signaling Pathway.
Int J Mol Sci
January 2025
Institute of Biomedicine & Department of Cell Biology, College of Life Science and Technology, Jinan University, Guangzhou 510632, China.
Following the COVID-19 pandemic, the prevalence of pulmonary fibrosis has increased significantly, placing patients at higher risk and presenting new therapeutic challenges. Current anti-fibrotic drugs, such as Nintedanib, can slow the decline in lung function, but their severe side effects highlight the urgent need for safer and more targeted alternatives. This study explores the anti-fibrotic potential and underlying mechanisms of an endogenous peptide (P5) derived from fibroblast growth factor 2 (FGF2), developed by our research team.
View Article and Find Full Text PDFADAR Therapeutics as a New Tool for Personalized Medicine.
Genes (Basel)
January 2025
Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy.
In the field of RNA therapy, innovative approaches based on adenosine deaminases acting on RNA (ADAR)-mediated site-directed RNA editing (SDRE) have been established, providing an exciting opportunity for RNA therapeutics. ADAR1 and ADAR2 enzymes are accountable for the predominant form of RNA editing in humans, which involves the hydrolytic deamination of adenosine (A) to inosine (I). This inosine is subsequently interpreted as guanosine (G) by the translational and splicing machinery because of their structural similarity.
View Article and Find Full Text PDFEvolutionary and Structural Insights into the RNA Polymerase I A34 Protein Family: A Focus on Intrinsic Disorder and Phase Separation.
Genes (Basel)
January 2025
Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
Background: Eukaryotic RNA polymerase I consists of 12 or 11 core subunits and three dissociable subunits, Rrn3, A34, and A49. The A34 and A49 subunits exist as a heterodimer. In silico analysis of the A34 family of transcription factors demonstrates a commonly shared domain structure despite a lack of sequence conservation, as well as N-terminal and C-terminal disordered regions.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!