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Mechanism-guided engineering of a minimal biological particle for genome editing.
Proc Natl Acad Sci U S A
January 2025
Innovative Genomics Institute, University of California, Berkeley, CA 94720.
The widespread application of genome editing to treat and cure disease requires the delivery of genome editors into the nucleus of target cells. Enveloped delivery vehicles (EDVs) are engineered virally derived particles capable of packaging and delivering CRISPR-Cas9 ribonucleoproteins (RNPs). However, the presence of lentiviral genome encapsulation and replication proteins in EDVs has obscured the underlying delivery mechanism and precluded particle optimization.
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 PDFUnlocking the catalytic precision of ligand-controlled enzymatic halogenation.
Proc Natl Acad Sci U S A
January 2025
School of Biomolecular Science and Engineering, Vidyasirimedhi Institute of Science and Technology (VISTEC), Rayong 10120, Thailand.
A single-component flavin-dependent halogenase, AetF, has emerged as an attractive biocatalyst for catalyzing halogenation. However, its flavin chemistry remains unexplored and cannot be predicted due to its uniqueness in sequence and structure compared to other flavin-dependent monooxygenases. Here, we investigated the flavin reactions of AetF using transient kinetics.
View Article and Find Full Text PDFAnti-Mycobacterial Activity of Bacterial Topoisomerase Inhibitors with Dioxygenated Linkers.
ACS Infect Dis
January 2025
Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, Colorado 80523, United States.
Developing new classes of drugs that are active against infections caused by is a priority for treating and managing this deadly disease. Here, we describe screening a small library of 20 DNA gyrase inhibitors and identifying new lead compounds. Three structurally diverse analogues were identified with minimal inhibitory concentrations of 0.
View Article and Find Full Text PDFSynthesis and Biological Evaluation of a New Biphenyl-Based Organogold(III) Complex with In Vitro and In Vivo Anticancer Activity.
J Med Chem
January 2025
Sorbonne Université, CNRS Institut Parisien de Chimie Moléculaire, IPCM, F-75005 Paris, France.
Despite recent advances in cancer treatment, there is still a need for novel compounds with antineoplastic activity. Among 11 biphenyl-based organogold(III) -heterocyclic carbene (NHC) (BGC) complexes of general formula [(C^C)Au(NHC-pyr)X], where (C^C) = 4,4'-ditertbutylbiphenyl, X = Cl or phenylacetylide, and (NHC-pyr) is a pyridyl-substituted NHC ligand, the complex bearing a 4-CF-pyridyl substituent and a chloride ligand showed promising antineoplastic activity on the triple negative breast cancer cell line. was able to induce cell apoptosis but had no effect on the cell cycle.
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