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The allosteric modulation of the structural dynamics of double-stranded DNA (dsDNA) duplexes as a function of distance from the site of a minor groove binding ligand is reported. Time-resolved temperature-jump infrared spectroscopy is used to interrogate the impact of binding a pyrrole-imidazole polyamide to dsDNA sequences 8-14 base-pairs in length. Our results demonstrate that the binding of the hairpin polyamide to its target site (5'-WWGTACW-3'; W = A/T) causes a marked suppression of structural dynamics, such as end fraying, with suppression observed in both the 3' and 5' directions. Quantitative analysis of end fraying suppression reveals a propagation length for dynamic modulation of 30 base-pairs. Identifying the structural impact of minor groove binding to dsDNA sequences furthers our understanding of the influence of dsDNA recognition and informs the design of next-generation synthetic transcription factors.
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http://dx.doi.org/10.1021/acs.jpclett.5c01542 | DOI Listing |
Phys Chem Chem Phys
September 2025
School of Chemistry and Chemical Engineering, University of Jinan, Jinan 250022, P. R. China.
The COVID-19 pandemic remains a global health crisis, with successive SARS-CoV-2 variants exhibiting enhanced transmissibility and immune evasion. Notably, the Omicron variant harbors extensive mutations in the spike protein's receptor-binding domain (RBD), altering viral fitness. While temperature is a critical environmental factor modulating viral stability and transmission, its molecular-level effects on variant-specific RBD-human angiotensin-converting enzyme 2 (hACE2) interactions remain underexplored.
View Article and Find Full Text PDFNat Prod Res
March 2025
Department of Pharmacology and Therapeutics, College of Pharmacy, Kuwait University, Safat, Kuwait.
The effects of apigenin, a plant flavonoid, were investigated using the two-electrode voltage-clamp technique on the function of the cloned α7 subunit of the human nicotinic acetylcholine (α7-nACh) receptor expressed in oocytes. Currents induced by ACh (100 μM) were reversibly potentiated by apigenin with an EC value of 5.4 µM in a voltage-independent manner.
View Article and Find Full Text PDFPestic Biochem Physiol
November 2025
Corteva Agriscience, Indianapolis, IN 46268, USA; Retired - Present address Agrilucent LLC, Morro Bay, CA 93442, USA.
Since their registration more than 25 years ago, the spinosyns have become a significant insect management tool in farmers' battles to protect crop quality and yield. Spinosad (Qalcova™ active) and spinetoram (Jemvelva™ active), the two members of the Insecticide Resistance Action Committee (IRAC) Group 5 nicotinic acetylcholine receptor (nAChR) allosteric modulators Site I, class of insecticides, have proven highly effective at controlling chewing insect pests on over 250 different crops. Their importance as an integral rotation partner in insect pest management programs has stimulated a large body of research into their mode of action (MoA) and mechanisms of resistance.
View Article and Find Full Text PDFMol Psychiatry
September 2025
Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, King's College London, 16 De Crespigny Park, London, SE5 8AB, UK.
Disrupted gamma-aminobutyric acid (GABA) neurotransmission may contribute to the pathophysiology of schizophrenia. Reductions in hippocampal GABAergic neurons have been found in schizophrenia, and increased hippocampal perfusion has been described in schizophrenia and in people at clinical high-risk for psychosis (CHRp). We have also found decreases in hippocampal GABA receptors containing the α5 subunit (GABARα5) in a well-validated neurodevelopmental rat model of relevance for schizophrenia.
View Article and Find Full Text PDFDrug Discov Today
September 2025
Department of Pharmaceutical and Artificial-Intelligence Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; Key Laboratory of Protection, Development and Utilization of Medicinal Resources in Liupanshan Area, Ministry of Education, Peptide & Protein Drug Research Cen
The landscape of allosteric drug discovery is undergoing a transformative shift, driven by the integration of three computational approaches: machine learning (ML), molecular dynamics (MD) simulations, and network theory. ML identifies potential allosteric sites from multidimensional biological datasets; MD simulations, empowered by enhanced sampling algorithms, reveal transient conformational states; and network analyses uncover communication pathways, further aiding in site identification. Their synergy enables rational allosteric modulator design.
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