DNA Minor Groove-Induced <i>cis</i>–<i>trans</i> Isomerization of a Near-Infrared Fluorescent Probe

Ganguly, S.N.; Murugan, N.; Ghosh, Debasis; Narayanaswamy, Nagarjun; Govindaraju, T.; Basu, Gautam

doi:10.1021/acs.biochem.1c00281

Cited by 6 publications

(4 citation statements)

References 75 publications

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“…Once the model is trained on MIM-NMR chemical shifts, we used it directly to predict NMR chemical shifts for a test set of eight new nucleic acids with sizes ranging from 600 to 900 atoms (Figure ). A short description about these nucleic acids with PDB ID’s 5IZP, 5ZLD, 2M3P, 1JS7, 1K8L, 5UZF, 6DM7, and 7BFX can be found in Table .…”

Section: Resultsmentioning

confidence: 99%

MIM-ML: A Novel Quantum Chemical Fragment-Based Random Forest Model for Accurate Prediction of NMR Chemical Shifts of Nucleic Acids

Chandy,

Raghavachari

2023

J. Chem. Theory Comput.

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We developed a random forest machine learning (ML) model for the prediction of 1 H and 13 C NMR chemical shifts of nucleic acids. Our ML model is trained entirely on reproducing computed chemical shifts obtained previously on 10 nucleic acids using a Molecules-in-Molecules (MIM) fragment-based density functional theory (DFT) protocol including microsolvation effects. Our ML model includes structural descriptors as well as electronic descriptors from an inexpensive low-level semiempirical calculation (GFN2-xTB) and trained on a relatively small number of DFT chemical shifts (2080 1 H chemical shifts and 1780 13 C chemical shifts on the 10 nucleic acids). The ML model is then used to make chemical shift predictions on 8 new nucleic acids ranging in size from 600 to 900 atoms and compared directly to experimental data. Though no experimental data was used in the training, the performance of our model is excellent (mean absolute deviation of 0.34 ppm for 1 H chemical shifts and 2.52 ppm for 13 C chemical shifts for the test set), despite having some nonstandard structures. A simple analysis suggests that both structural and electronic descriptors are critical for achieving reliable predictions. This is the first attempt to combine ML from fragment-based DFT calculations to predict experimental chemical shifts accurately, making the MIM-ML model a valuable tool for NMR predictions of nucleic acids.

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Section: Resultsmentioning

confidence: 99%

MIM-ML: A Novel Quantum Chemical Fragment-Based Random Forest Model for Accurate Prediction of NMR Chemical Shifts of Nucleic Acids

Chandy,

Raghavachari

2023

J. Chem. Theory Comput.

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“…The fluorescence data, consistent with the absorption data, demonstrated that the specific DNA-binding mode of 6d is sequence sensitive and very different for CG versus AT stretches. The origin of the difference probably lies in the much stronger preference of AT stretches to favor minor groove binding . For DNA containing CG stretches, the most probable DNA-binding mode is nonspecific surface binding, while for DNA containing AT stretches an additional minor groove binding mode is introduced, making the binding heterogeneous.…”

Section: Resultsmentioning

confidence: 99%

Sequence-Specific Dual DNA Binding Modes and Cytotoxicities of N-6-Functionalized Norcryptotackieine Alkaloids

et al. 2023

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Norcryptotackieine (1a) belongs to the indoloquinoline class of alkaloids isolated from Cryptolepis sanguinolenta, a plant species that has been traditionally used as an antimalarial agent. Additional structural modifications of 1a can potentially enhance its therapeutic potency. Indoloquinolines such as cryptolepine, neocryptolepine, isocryptolepine, and neoisocryptolepine show restricted clinical applications owing to their cytotoxicity deriving from interactions with DNA. Here, we examined the effect of substitutions at the N-6 position of norcryptotackieine on the cytotoxicity, as well as structure–activity relationship studies pertaining to sequence specific DNA-binding affinities. The representative compound 6d binds DNA in a nonintercalative/pseudointercalative fashion, in addition to nonspecific stacking on DNA, in a sequence selective manner. The DNA-binding studies clearly establish the mechanism of DNA binding by N-6-substituted norcryptotackieines and neocryptolepine. The synthesized norcryptotackieines 6c,d and known indoloquinolines were screened on different cell lines (HEK293, OVCAR3, SKOV3, B16F10, and HeLa) to assess their cytotoxicity. Norcryptotackieine 6d (IC50 value of 3.1 μM) showed 2-fold less potency when compared to the natural indoloquinoline cryptolepine 1c (IC50 value of 1.64 μM) in OVCAR3 (ovarian adenocarcinoma) cell lines.

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“…They also showed that the probe could be applied to specific parasite staining and treatment. Recently, they have explained the cis/trans isomerization of QCy-DT upon binding to DNA targets and promoted the application of the probe [ 39 ]. Pang’s group developed a novel NIR-emitting probe based on phenol-containing m-phenylene building blocks for DNA-targeted staining through a groove binding mechanism ( 4 , Scheme 1 ).…”

Section: Design Of Molecular Probes For Organelle-targeted Cell Imagingmentioning

confidence: 99%

Recent Development of Advanced Fluorescent Molecular Probes for Organelle-Targeted Cell Imaging

Dai

Cui

et al. 2023

Biosensors

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Fluorescent molecular probes are very powerful tools that have been generally applied in cell imaging in the research fields of biology, pathology, pharmacology, biochemistry, and medical science. In the last couple of decades, numerous molecular probes endowed with high specificity to particular organelles have been designed to illustrate intracellular images in more detail at the subcellular level. Nowadays, the development of cell biology has enabled the investigation process to go deeply into cells, even at the molecular level. Therefore, probes that can sketch a particular organelle’s location while responding to certain parameters to evaluate intracellular bioprocesses are under urgent demand. It is significant to understand the basic ideas of organelle properties, as well as the vital substances related to each unique organelle, for the design of probes with high specificity and efficiency. In this review, we summarize representative multifunctional fluorescent molecular probes developed in the last decade. We focus on probes that can specially target nuclei, mitochondria, endoplasmic reticulums, and lysosomes. In each section, we first briefly introduce the significance and properties of different organelles. We then discuss how probes are designed to make them highly organelle-specific. Finally, we also consider how probes are constructed to endow them with additional functions to recognize particular physical/chemical signals of targeted organelles. Moreover, a perspective on the challenges in future applications of highly specific molecular probes in cell imaging is also proposed. We hope that this review can provide researchers with additional conceptual information about developing probes for cell imaging, assisting scientists interested in molecular biology, cell biology, and biochemistry to accelerate their scientific studies.

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DNA Minor Groove-Induced cis–trans Isomerization of a Near-Infrared Fluorescent Probe

Cited by 6 publications

References 75 publications

MIM-ML: A Novel Quantum Chemical Fragment-Based Random Forest Model for Accurate Prediction of NMR Chemical Shifts of Nucleic Acids

MIM-ML: A Novel Quantum Chemical Fragment-Based Random Forest Model for Accurate Prediction of NMR Chemical Shifts of Nucleic Acids

Sequence-Specific Dual DNA Binding Modes and Cytotoxicities of N-6-Functionalized Norcryptotackieine Alkaloids

Recent Development of Advanced Fluorescent Molecular Probes for Organelle-Targeted Cell Imaging

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