Short contiguous arrays of variant CTAGGG repeats in the human telomere are unstable in the male germline and somatic cells, suggesting formation of unusual structures by this repeat type. Here, we report on the structure of an intramolecular G-quadruplex formed by DNA sequences containing four human telomeric variant CTAGGG repeats in potassium solution. Our results reveal a new robust antiparallel G-quadruplex fold involving two G-tetrads sandwiched between a G.C base pair and a G.C.G.C tetrad, which could represent a new platform for drug design targeted to human telomeric DNA.
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http://dx.doi.org/10.1093/nar/gkp630 | DOI Listing |
Int J Mol Sci
December 2024
LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal.
Cancer is a leading cause of death, so continuous efforts into cancer therapy are imperative. In tumor cells, telomerase and oncogene activity are key points for uncontrolled cell growth. Targeting these processes with ligands that inhibit telomerase and/or reduce oncogene expression has been identified as a promising cancer therapy.
View Article and Find Full Text PDFMedicina (Kaunas)
November 2024
Respiratory Disease Unit, University Hospital of Modena, 41124 Modena, Italy.
Recent advances in genetics and epigenetics have provided critical insights into the pathogenesis of both idiopathic and non-idiopathic interstitial lung diseases (ILDs). Mutations in telomere-related genes and surfactant proteins have been linked to familial pulmonary fibrosis, while variants in MUC5B and TOLLIP increase the risk of ILD, including idiopathic pulmonary fibrosis and rheumatoid arthritis-associated ILD. Epigenetic mechanisms, such as DNA methylation, histone modifications, and non-coding RNAs such as miR-21 and miR-29, regulate fibrotic pathways, influencing disease onset and progression.
View Article and Find Full Text PDFInt J Environ Res Public Health
December 2024
Center for Healthy Aging, Self-Management and Complex Care, College of Nursing, The Ohio State University, Columbus, OH 43210, USA.
Background: Gastrointestinal (GI) distress is prevalent and often persistent among cancer survivors, impacting their quality of life, nutrition, daily function, and mortality. GI health screening is crucial for preventing and managing this distress. However, accurate classification methods for GI health remain unexplored.
View Article and Find Full Text PDFFoods
December 2024
Department of Genetics, Faculty of Agriculture, Alexandria University, Alexandria 21545, Egypt.
Oxidative stress can disrupt the body's ability to fight harmful free radicals, leading to premature aging and various health complications. This study investigated the antioxidant and anti-aging properties of four medicinal and edible mushrooms: , , , and . The antioxidant activity of mushroom extracts was evaluated using (DPPH-ABTS-Reducing power).
View Article and Find Full Text PDFBiomolecules
December 2024
Department of Medical Biochemistry, Faculty of Medicine, Hacettepe University, Ankara 06100, Turkey.
Telomerase and telomeres are crucial in cancer cell immortalization, making them key targets for anticancer therapies. Currently, 6-thio-dG (THIO) combined with the anti-PD-1 inhibitor Cemiplimab is under phase II clinical investigation (NCT05208944) in NSCLC patients resistant to prior immunotherapies. This study presents the design, synthesis, and evaluation of novel bimodular conjugate molecules combining telomere-targeting nucleoside analogs and phosphatidyl diglyceride groups.
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