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In conventional dendrimer synthesis, producing defective dendrimers is unavoidable. However, no synthetic method exists to prepare these defect dendrimers with a well-defined structure. A novel and efficient solid-phase method has been developed to synthesize well-defined lysine defect dendrimers using orthogonally protected lysine residues. This chapter details the synthesis of two defect lysine dendrimers. Additionally, the synthesis of a boronic acid-decorated defect lysine dendrimer is presented to demonstrate the feasibility of this method for preparing functional defect dendrimers.
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http://dx.doi.org/10.1007/978-1-0716-4562-8_14 | DOI Listing |
Life Sci Alliance
December 2025
Department of Medicine, University of Wisconsin-Madison, Madison, WI, USA
Nε-lysine acetylation in the lumen of the ER requires two acetyltransferases, ATase1/NAT8B and ATase2/NAT8. They are type II membrane proteins and belong to the larger GNAT superfamily of acetyltransferases. Their enzymatic activity is tightly coupled to the import of acetyl-CoA in the lumen of the ER by AT-1/SLC33A1.
View Article and Find Full Text PDFNucleic Acids Res
September 2025
Division of Chromatin Regulation, National Institute for Basic Biology, Okazaki 444-8585, Japan.
Methylation of histone H3 at lysine 9 (H3K9me), a hallmark of heterochromatin, is catalyzed by Clr4/Suv39. Clr4/Suv39 contains two conserved domains-an N-terminal chromodomain and a C-terminal catalytic domain-connected by an intrinsically disordered region (IDR). Several mechanisms have been proposed to regulate Clr4/Suv39 activity, but how it is regulated under physiological conditions remains largely unknown.
View Article and Find Full Text PDFCell Rep
September 2025
Virginia Tech Fralin Biomedical Research Institute Cancer Research Center DC, Children's National Research & Innovation Campus, Washington, DC, USA; Department of Biomedical Sciences and Pathobiology (DBSP), Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, USA; Center
Nuclear receptor binding set domain protein 1 (NSD1) is a key histone methyltransferase that catalyzes di-methylation of lysine 36 of histone H3 (H3K36me2), essential for active chromatin domains. While the loss of NSD1 activity halts embryonic development and its aberrant gain drives oncogenesis in leukemia and glioma, the regulatory mechanisms remain poorly understood. Here, we uncover that NSD1 requires allosteric activation through the aromatic pocket of its Pro-Trp-Trp-Pro 2 (PWWP2) domain.
View Article and Find Full Text PDFBackground Over 300 mutations in have been identified as causes of early-onset Alzheimer's disease (EOAD). While these include missense mutations and a few insertions, deletions, or duplications, none result in open reading frame shifts, and all alter γ-secretase function to increase the long/short Aβ ratio. Methods We identified a novel heterozygous nonsense variant, c.
View Article and Find Full Text PDFbioRxiv
August 2025
Rutgers Cancer Institute, New Brunswick, New Jersey, USA.
In most solid tumors, hypoxia constitutes a defining microenvironmental feature that reprograms malignant cells into a highly metastatic state by driving cellular plasticity and exacerbating chromosomal instability (CIN). However, the mechanisms by which cancer cells concurrently co-opt these elements of hypoxic adaptation to promote metastasis remains poorly understood. Here, we report that hypoxia promotes metastasis by suppressing the JmjC-containing histone lysine demethylase Kdm8.
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