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Binding mode-guided development of high-performance antibodies targeting site-specific posttranslational modifications.
Proc Natl Acad Sci U S A
January 2025
Laura and Isaac Perlmutter Cancer Center, New York University Langone Health, New York, NY 10016.
Posttranslational modifications (PTMs) of proteins play critical roles in regulating many cellular events. Antibodies targeting site-specific PTMs are essential tools for detecting and enriching PTMs at sites of interest. However, fundamental difficulties in molecular recognition of both PTM and surrounding peptide sequence have hindered the efficient generation of highly sequence-specific anti-PTM antibodies.
View Article and Find Full Text PDFPsDMAP1/PsTIP60-regulated H4K16ac is required for ROS-dependent virulence adaptation of on host plants.
Proc Natl Acad Sci U S A
January 2025
Department of Plant Pathology, College of Plant Protection, China Agricultural University, Beijing 100193, China.
Host plants and various fungicides inhibit plant pathogens by inducing the release of excessive reactive oxygen species (ROS) and causing DNA damage, either directly or indirectly leading to cell death. The mechanisms by which the oomycete manages ROS stress resulting from plant immune responses and fungicides remains unclear. This study elucidates the role of histone acetylation in ROS-induced DNA damage responses (DDR) to adapt to stress.
View Article and Find Full Text PDFComputational-aided rational mutation design of pertuzumab to overcome active HER2 mutation S310F through antibody-drug conjugates.
Proc Natl Acad Sci U S A
January 2025
Laboratory of Precision Medicine and Biopharmaceuticals, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
Recurrent missense mutations in the human epidermal growth factor receptor 2 (HER2) have been identified across various human cancers. Among these mutations, the active S310F mutation in the HER2 extracellular domain stands out as not only oncogenic but also confers resistance to pertuzumab, an antibody drug widely used in clinical cancer therapy, by impeding its binding. In this study, we have successfully employed computational-aided rational design to undertake directed evolution of pertuzumab, resulting in the creation of an evolved pertuzumab variant named Ptz-SA.
View Article and Find Full Text PDFRecent Advances in Strategies to Enhance Photodynamic and Photothermal Therapy Performance of Single-Component Organic Phototherapeutic Agents.
Adv Sci (Weinh)
January 2025
The Department of Medical Imaging, The Affiliated Guangdong Second Provincial General Hospital of Jinan University, Xingangzhong Road 466, Guangzhou, 518037, P. R. China.
Photodynamic therapy (PDT) and photothermal therapy (PTT) have emerged as promising treatment options, showcasing immense potential in addressing both oncologic and nononcologic diseases. Single-component organic phototherapeutic agents (SCOPAs) offer advantages compared to inorganic or multicomponent nanomedicine, including better biosafety, lower toxicity, simpler synthesis, and enhanced reproducibility. Nonetheless, how to further improve the therapeutic effectiveness of SCOPAs remains a challenging research area.
View Article and Find Full Text PDFSonogenetics is a novel antiarrhythmic mechanism.
Chaos
January 2025
School of Physics and Information Technology, Shaanxi Normal University, Xi'an 710062, China.
Arrhythmia of the heart is a dangerous and potentially fatal condition. The current widely used treatment is the implantable cardioverter defibrillator (ICD), but it is invasive and affects the patient's quality of life. The sonogenetic mechanism proposed here focuses ultrasound on a cardiac tissue, controls endogenous stretch-activated Piezo1 ion channels on the focal region's cardiomyocyte sarcolemma, and restores normal heart rhythm.
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