Fluorescent base analogs (FBAs) are powerful probes of nucleic acids' structures and dynamics. However, previously reported FBAs exhibit relatively low brightness and therefore limited sensitivity of detection. Here we report the hitherto brightest FBA that has ideal molecular rotor properties for detecting local dynamic motions associated with base pair mismatches. The new -stilbene annulated uracil derivative "T" exhibits bright fluorescence emissions in various solvents (ε × Φ = 3400-29 700 cm M) and is highly sensitive to mechanical motions in duplex DNA (ε × Φ = 150-4250 cm M). T is thereby a "smart" thymidine analog, exhibiting a 28-fold brighter fluorescence intensity when base paired with A as compared to T or C. Time-correlated single photon counting revealed that the fluorescence lifetime of T (τ = 4-11 ns) was shorter than its anisotropy decay in well-matched duplex DNA (θ = 20 ns), yet longer than the dynamic motions of base pair mismatches (0.1-10 ns). These properties enable unprecedented sensitivity in detecting local dynamics of nucleic acids.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1021/jacs.0c05180 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Integrating structure-guided and fragment-based inhibitor design to combat bedaquiline resistant : a molecular dynamics study.
J Biomol Struct Dyn
December 2024
Amity Institute of Biotechnology, Amity University, Kolkata, India.
The first FDA approved, MDR-TB inhibitory drug bedaquiline (BDQ), entraps the c-ring of the proton-translocating F region of enzyme ATP synthase of , thus obstructing successive ATP production. Present-day BDQ-resistance has been associated with cardiotoxicity and mutation(s) in the atpE gene encoding the c subunit of ATP synthase (ATPc) generating five distinct ATPc mutants: Ala63→Pro, Ile66→Met, Asp28→Gly, Asp28→Val and Glu61→Asp. We created three discrete libraries, first by repurposing bedaquiline via scaffold hopping approach, second one having natural plant compounds and the third being experimentally derived analogues of BDQ to identify one drug candidate that can inhibit ATPc activity more efficiently with less toxic properties.
View Article and Find Full Text PDFBackground: Flecainide and other class-Ic antiarrhythmic drugs (AADs) are widely used in Andersen-Tawil syndrome type 1 (ATS1) patients. However, class-Ic drugs might be proarrhythmic in some cases. We investigated the molecular mechanisms of class-I AADs proarrhythmia and whether they might increase the risk of death in ATS1 patients with structurally normal hearts.
View Article and Find Full Text PDFShifting CH/CO Adsorption and Separation in Pillar-Layered Metal-Organic Frameworks Finely-Regulated by Molecular Rotation.
Small
December 2024
Key Laboratory of Macromolecular Science of Shaanxi Province, School of Chemistry & Chemical Engineering, Shaanxi Normal University, Xi'an, 710062, China.
The efficient separation of C₂H₂/CO₂ mixture is crucial for industrial applications. A promising strategy is proposed herein to fine-tune the C₂H₂/CO adsorption and separation by pillar-layered metal-organic framework (MOF) adsorbents via molecular rotation. Keeping the same ultramicroporous architecture, three Zn-X-TRZ (TRZ = 1,2,4-triazole) adsorbents are prepared with X-pillar rotors varying from 9,10-anthracenedicarboxylic acid (ADC), 1,4-naphthalenedicarboxylic acid (NDC) to 1,4-benzenedicarboxylic acid (BDC).
View Article and Find Full Text PDFQuantum Tunneling: History and Mystery of Large Amplitude Motions over a Century.
J Phys Chem Lett
December 2024
Univ Paris Est Creteil and Université Paris Cité, CNRS, LISA, F-94010 Créteil, France.
Large amplitude motions (LAMs), most notably represented by proton tunneling, mark a significant departure from small amplitude vibrations where protons merely oscillate around their equilibrium positions. These substantial displacements require tunneling through potential energy barriers, leading to splittings in, e.g.
View Article and Find Full Text PDFLipid droplet specific BODIPY based rotors with viscosity sensitivity to distinguish normal and cancer cells: impact of molecular conformation.
J Mater Chem B
December 2024
Main group Organometallics Optoelectronic Materials and Catalysis lab, Department of Chemistry, National Institute of Technology, Calicut, 673601, India.
Lipid droplets (LDs) are dynamic, multifunctional organelles critical for regulating energy balance, cell signaling, membrane formation, and trafficking. Recent studies have highlighted LDs as emerging cancer biomarkers, with cancer cells typically exhibiting a higher number and viscosity of LDs compared to normal cells. This discovery paves the way for developing molecular probes that can monitor intracellular viscosity changes within LDs, offering a powerful tool for early cancer diagnosis, recurrence monitoring, and therapeutic interventions.
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!