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Leveraging Structural and Computational Biology for Molecular Glue Discovery.
J Med Chem
January 2025
Experimental Drug Development Centre, Chromos, Agency for Science, Technology and Research, 10 Biopolis Road, #05-01, Singapore 138670.
The discovery of molecular glues has made significant strides, unlocking new avenues for targeted protein degradation as a therapeutic strategy, thereby expanding the scope of drug discovery into territories previously considered undruggable. Pioneering molecules like thalidomide and its derivatives have paved the way for the development of small molecules that can induce specific protein degradation by hijacking the cellular ubiquitin-proteasome system. Recent advancements have focused on expanding the range of E3 ligases and target proteins that can be modulated by molecular glues.
View Article and Find Full Text PDFNovel mutations found in genes involved in global developmental delay and intellectual disability by whole-exome sequencing, homology modeling, and systems biology.
World J Biol Psychiatry
January 2025
Division of Genetics, Department of Cell and Molecular Biology and Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, Iran.
Background: Genes associated with global developmental delay (GDD) and intellectual disability (ID) are increasingly being identified through next-generation sequencing (NGS) technologies. This study aimed to identify novel mutations in GDD/ID phenotypes through whole-exome sequencing (WES) and additional analyses.
Material And Methods: WES was performed on 27 subjects, among whom 18 were screened for potential novel mutations.
Improvement in XIa Selectivity of Snake Venom Peptide Analogue BF9-N17K Using P2' Amino Acid Replacements.
Toxins (Basel)
January 2025
Institute of Biomedicine, Hubei Key Laboratory of Embryonic Stem Cell Research, College of Basic Medicine, Hubei University of Medicine, Shiyan 442000, China.
Coagulation factor XIa is a new serine-protease family drug target for next-generation anticoagulants. With the snake venom Kunitz-type peptide BF9 as the scaffold, we obtained a highly active XIa inhibitor BF9-N17K in our previous work, but it also inhibited the hemostatic target plasmin. Here, in order to enhance the selectivity of BF9-N17K toward XIa, four mutants, BF9-N17K-L19A, BF9-N17K-L19S, BF9-N17K-L19D, and BF9-N17K-L19K, were further designed using the P2' amino acid classification scanning strategy.
View Article and Find Full Text PDFAntigen Delivery Platforms for Next-Generation Coronavirus Vaccines.
Vaccines (Basel)
December 2024
Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, School of Medicine, University of California Irvine, Irvine, CA 92697, USA.
The COVID-19 pandemic, caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is in its sixth year and is being maintained by the inability of current spike-alone-based COVID-19 vaccines to prevent transmission leading to the continuous emergence of variants and sub-variants of concern (VOCs). This underscores the critical need for next-generation broad-spectrum pan-Coronavirus vaccines (pan-CoV vaccine) to break this cycle and end the pandemic. The development of a pan-CoV vaccine offering protection against a wide array of VOCs requires two key elements: (1) identifying protective antigens that are highly conserved between passed, current, and future VOCs; and (2) developing a safe and efficient antigen delivery system for induction of broad-based and long-lasting B- and T-cell immunity.
View Article and Find Full Text PDFElectroencephalographic and Epilepsy Findings in ZNF711 Variants: A Case Series of Two Siblings.
Neurol Int
January 2025
Clinical Pediatrics, Department of Molecular Medicine and Development, University of Siena, Azienda Ospedaliero-Universitaria Senese, 53100 Siena, Italy.
Background/objectives: ZNF711(Zinc finger protein 711) encodes a zinc finger protein of currently undefined function, located on the X chromosome. Current knowledge includes a limited number of case reports where this gene has been exclusively associated with X-linked intellectual disability (XLID). As far as we are aware, we report the first cases of epilepsy associated with this particular variant.
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