Helical aromatic oligoamide foldamers bearing anionic side chains that mimic the overall shape and charge surface distribution of DNA were synthesized. Their interactions with chromosomal protein Sac7d, a non-sequence-selective DNA-binder that kinks DNA, were investigated by Surface Plasmon Resonance (SPR), Isothermal Titration Calorimetry (ITC), Circular Dichroism spectroscopy (CD), melting curve analysis, Atomic Force Microscopy (AFM), and Nuclear Magnetic Resonance (NMR), as well as by single crystal X-ray crystallography. The foldamers were shown to bind to Sac7d better than a DNA duplex of comparable length. The interaction is diastereoselective and takes place at the DNA binding site. Crystallography revealed that the DNA mimic foldamers have a binding mode of their own and that they can bind to Sac7d without being kinked.
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http://dx.doi.org/10.1002/anie.202422958 | DOI Listing |
Angew Chem Int Ed Engl
December 2024
Université de Bordeaux, CBMN UMR5248, IECB, 2, rue Robert Escarpit, 33607, PESSAC, FRANCE.
Peptide stapling has emerged as a versatile approach in drug discovery to reinforce secondary structure elements especially α-helices and improve properties of linear bioactive peptides. Inspired by the prevalence of arginine in protein-protein and protein-DNA interfaces, we investigated guanidinium-stapling as a means to constrain helical peptides. Guanidinium stapling was readily achieved on solid support, utilizing two orthogonally protected lysine or unatural α-amino acid residues with an amino function.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
December 2024
Ludwig-Maximilians-Universitat Munchen, Pharmacy, Butenandtstraße 5 - 13, 81377, Munich, GERMANY.
Helical aromatic oligoamide foldamers bearing anionic side chains that mimic the overall shape and charge surface distribution of DNA were synthesized. Their interactions with chromosomal protein Sac7d, a non-sequence-selective DNA-binder that kinks DNA, were investigated by Surface Plasmon Resonance (SPR), Isothermal Titration Calorimetry (ITC), Circular Dichroism spectroscopy (CD), melting curve analysis, Atomic Force Microscopy (AFM), and Nuclear Magnetic Resonance (NMR), as well as by single crystal X-ray crystallography. The foldamers were shown to bind to Sac7d better than a DNA duplex of comparable length.
View Article and Find Full Text PDFACS Meas Sci Au
December 2024
Department of Chemistry, Oklahoma State University, Stillwater, Oklahoma 74078, United States.
This article presents a colorimetric visual biosensor designed for direct application in undiluted biofluids, which holds significant promise for point-of-need applications. Unlike traditional biosensors that struggle with heavily diluted sample matrices, the presented biosensor does not require any instrumentation or trained personnel, making it highly practical. The sensor features an oligonucleotide probe covalently attached to magnetically separable magnetite (FeO) particles.
View Article and Find Full Text PDFG3 (Bethesda)
December 2024
Department of Integrative Biology, University of Guelph, Guelph, Ontario, N1G 2W1.
The release of heavy metals from industrial, agricultural, and mining activities poses significant risks to aquatic ecosystems by degrading water quality and generating reactive oxygen species (ROS) that can damage DNA in aquatic organisms. Daphnia is a widespread keystone species in freshwater ecosystems that is routinely exposed to a range of anthropogenic and natural stressors. With a fully sequenced genome, a well-understood life history and ecology, and an extensive library of responses to toxicity, Daphnia serves as an ideal model organism for studying the impact of environmental stressors on genomic stability.
View Article and Find Full Text PDFBiol Pharm Bull
December 2024
Department of Laboratory Medicine, The People's Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical Sciences.
The aim of this study was to analyze dihydrolipoyllysine-residue acetyltransferase (DLAT) expression and diagnostic ability in hepatocellular carcinoma (HCC), assess its role in HCC growth, and factors affecting it. We conducted bioinformatics analyses, examined DLAT expression and prognosis in pre-cancer, and performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment studies while investigating its correlation with immunity. We also predicted regulatory factors, and detected DLAT in HCC cells using quantitative PCR (qPCR) and Western blotting, and in patient serum via enzyme-linked immunosorbent assay (ELISA).
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