In the search for new drug candidates for DNA recognition, affinity and sequence selectivity are two of the most important features. NMe-azathiocoraline, a synthetic antitumor bisintercalator derived from the natural marine product thiocoraline, shows similar potency to the parent compound, as well as possessing enhanced stability. Analysis of the DNA-binding selectivity of NMe-azathiocoraline by DNase I footprinting using universal substrates with all 136 tetranucleotides and all possible symmetrical hexanucleotide sequences revealed that, although this ligand binds to all CpG steps with lower affinities than thiocoraline, it displays additional binding to AT-rich sites. Moreover, fluorescence melting studies showed a strong interaction of the synthetic molecule with CACGTG and weaker binding to ACATGT and AGATCT. These findings demonstrate that NMe-azathiocoraline has the same mode of action as thiocoraline, mimicking its DNA-binding selectivity despite the substitution of its thioester bonds by NMe-amide bridges.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4027633 | PMC |
| http://dx.doi.org/10.1021/ml400323x | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Intestinal human carboxylesterase 2 (CES2) expression rescues drug metabolism and most metabolic syndrome phenotypes in global Ces2 cluster knockout mice.
Acta Pharmacol Sin
November 2024
Division of Pharmacology, The Netherlands Cancer Institute, 1066 CX, Amsterdam, The Netherlands.
Article Synopsis
- - Carboxylesterase 2 (CES2) is primarily found in the liver and intestine, playing a significant role in metabolizing various compounds, influencing drug effectiveness, and affecting lipid and glucose metabolism.
- - The study involved creating knockout mice lacking CES2 genes and transgenic mice with human CES2 to assess the effects of CES2 on drug metabolism and metabolic health.
- - Findings revealed that while the absence of CES2 led to fatty liver and metabolic issues, introducing human CES2, especially in the intestine, improved these conditions and could potentially address metabolic syndrome challenges.
Glutathione transferase P1 is modified by palmitate.
PLoS One
September 2024
Department of Physiology and Membrane Protein Disease Research Group, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada.
Article Synopsis
- GSTP1 is a versatile protein that helps protect cells from damaging substances, influences cell growth and death, and typically exists in the cytosol but can also associate with other cell compartments like the plasma membrane.
- The study investigates how GSTP1 undergoes palmitoylation, a process where a fatty acid attaches to the protein, and whether this affects its location and function within cells.
- Findings show that GSTP1 is modified by palmitate at multiple sites, including some non-Cys residues, and this modification allows it to exist in both membrane and cytosolic fractions, potentially impacting its various cellular roles.
Cell-Material Interactions in Covalent Adaptable Thioester Hydrogels.
ACS Biomater Sci Eng
September 2024
Davidson School of Chemical Engineering, Purdue University, West Lafayette, Indiana 47907, United States.
Covalent adaptable networks (CANs) are polymeric networks with cross-links that can break and reform in response to external stimuli, including pH, shear, and temperature, making them potential materials for use as injectable cell delivery vehicles. In the native niche, cells rearrange the extracellular matrix (ECM) to undergo basic functions including migration, spreading, and proliferation. Bond rearrangement enables these hydrogels to mimic viscoelastic properties of the native ECM which promote migration and delivery from the material to the native tissue.
View Article and Find Full Text PDFStructural basis for transthiolation intermediates in the ubiquitin pathway.
Nature
September 2024
Structural Biology Program, Sloan Kettering Institute, New York, NY, USA.
Transthiolation (also known as transthioesterification) reactions are used in the biosynthesis of acetyl coenzyme A, fatty acids and polyketides, and for post-translational modification by ubiquitin (Ub) and ubiquitin-like (Ubl) proteins. For the Ub pathway, E1 enzymes catalyse transthiolation from an E1~Ub thioester to an E2~Ub thioester. Transthiolation is also required for transfer of Ub from an E2~Ub thioester to HECT (homologous to E6AP C terminus) and RBR (ring-between-ring) E3 ligases to form E3~Ub thioesters.
View Article and Find Full Text PDFThe identification and expression analysis of walnut Acyl-ACP thioesterases.
Front Genet
July 2024
Key Laboratory of Agro-Products Quality and Safety of Xinjiang, Institute of Agricultural Quality Standards and Testing Technology, Xinjiang Academy of Agricultural Sciences, Ürümqi, China.
Walnuts ( L.), renowned for their nutritional potency, are a rich source of unsaturated fatty acids. Their regular intake plays a pivotal role in health maintenance and recuperation from a myriad of ailments.
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!