Unlocking Pb<sup>2+</sup> Sensing Potential in a DNA G-Quadruplex via Loop Modification with Fluorescent Chalcone Surrogates

Johnson, Ryan E.; Murray, Makay T.; Roby, Dylan J.; Bycraft, Lucas J.; Churcher, Zachary R.; Yadav, Saanya; Johnson, Philip E.; Wetmore, Stacey D.; Manderville, Richard A.

doi:10.1021/acssensors.3c01866

Cited by 2 publications

(1 citation statement)

References 41 publications

(86 reference statements)

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“…Monovalent cations such as K + and Na + exist, stabilizing the entire framework. [3,4] GQ-DNA-forming nucleic acid sequences have been identified in a variety of genomic locations, including telomeric ends and oncogene promoter regions. Such findings suggest that GQ structures may be critical for the control of several biological processes, such as telomere preservation, transcription, translation, replication and more.…”

Section: Introductionmentioning

confidence: 99%

Deciphering Preferential Binding Interaction of Synthetic Pyrido[2,3‐c]Carbazole Alkaloid Derivative (PCAD) with Pu24T G‐quadruplex DNA

Pal,

Bag,

Burman

et al. 2024

ChemistrySelect

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G‐quadruplex DNA (GQ‐DNA) represents one of the most significant non‐canonical nucleic acid configurations. GQ‐DNA producing sequences are found in different important genomic areas, including the promoter islands of numerous oncogenes and human telomere regions. Therefore, GQ‐DNA is a key target for anticancer medicines. GQ‐DNA has a highly variable structure, it is critical to develop ligand molecules that selectively target certain quadruplex sequences. Natural products such as pyridocarbazole alkaloids have grown interest for healthcare and medicinal values and they considered as a valuable source of innovative anticancer medicines among the chemical compounds. In this investigation, we have synthesised and characterized pyrido[2,3‐c]carbazole derivative (PCAD) through NMR and IR spectra and explore the interactions between PCAD and Pu24T GQ (promoter region), h‐TELO GQ (telomere region) and duplex DNA by employing several multi‐spectroscopic analytical techniques. We have found that PCAD preferentially interacts with Pu24T GQ DNA as compared to other DNA sequences. These findings highlights PCAD as an appealing option for targeting the Pu24T promoter region and consequently acting as an anti‐cancer drug. This study also highlights the potential for developing drugs to understand the molecular aspects of GQ DNA recognition and signaling, paving the way for future research on GQ biology.

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Section: Introductionmentioning

confidence: 99%

Deciphering Preferential Binding Interaction of Synthetic Pyrido[2,3‐c]Carbazole Alkaloid Derivative (PCAD) with Pu24T G‐quadruplex DNA

Pal,

Bag,

Burman

et al. 2024

ChemistrySelect

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Unlocking precision in aptamer engineering: a case study of the thrombin binding aptamer illustrates why modification size, quantity, and position matter

Murray,

Wetmore

2024

Nucleic Acids Research

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The thrombin binding aptamer (TBA) is a prototypical platform used to understand the impact of chemically-modified nucleotides on aptamer stability and target affinity. To provide structural insight into the experimentally-observed effects of modification size, location, and number on aptamer performance, long time-scale molecular dynamics (MD) simulations were performed on multiple binding orientations of TBA–thrombin complexes that contain a large, flexible tryptophan thymine derivative (T-W) or a truncated analogue (T-K). Depending on modification position, T-W alters aptamer–target binding orientations, fine-tunes aptamer–target interactions, strengthens networks of nucleic acid–protein contacts, and/or induces target conformational changes to enhance binding. The proximity and 5′-to-3′ directionality of nucleic acid structural motifs also play integral roles in the behavior of the modifications. Modification size can differentially influence target binding by promoting more than one aptamer–target binding pose. Multiple modifications can synergistically strengthen aptamer–target binding by generating novel nucleic acid–protein structural motifs that are unobtainable for single modifications. By studying a diverse set of modified aptamers, our work uncovers design principles that must be considered in the future development of aptamers containing chemically-modified nucleotides for applications in medicine and biotechnology, highlighting the value of computational studies in nucleic acids research.

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Unlocking Pb²⁺ Sensing Potential in a DNA G-Quadruplex via Loop Modification with Fluorescent Chalcone Surrogates

Cited by 2 publications

References 41 publications

Deciphering Preferential Binding Interaction of Synthetic Pyrido[2,3‐c]Carbazole Alkaloid Derivative (PCAD) with Pu24T G‐quadruplex DNA

Deciphering Preferential Binding Interaction of Synthetic Pyrido[2,3‐c]Carbazole Alkaloid Derivative (PCAD) with Pu24T G‐quadruplex DNA

Unlocking precision in aptamer engineering: a case study of the thrombin binding aptamer illustrates why modification size, quantity, and position matter

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Unlocking Pb2+ Sensing Potential in a DNA G-Quadruplex via Loop Modification with Fluorescent Chalcone Surrogates

Cited by 2 publications

References 41 publications

Deciphering Preferential Binding Interaction of Synthetic Pyrido[2,3‐c]Carbazole Alkaloid Derivative (PCAD) with Pu24T G‐quadruplex DNA

Deciphering Preferential Binding Interaction of Synthetic Pyrido[2,3‐c]Carbazole Alkaloid Derivative (PCAD) with Pu24T G‐quadruplex DNA

Unlocking precision in aptamer engineering: a case study of the thrombin binding aptamer illustrates why modification size, quantity, and position matter

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Unlocking Pb²⁺ Sensing Potential in a DNA G-Quadruplex via Loop Modification with Fluorescent Chalcone Surrogates