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Identification of novel 7-hydroxycoumarin derivatives as ELOC binders with potential to modulate CRL2 complex formation.
Sci Rep
January 2025
Research Institute, National Cancer Center, Goyang-si, 10408, Gyeonggi, Republic of Korea.
The VHL-containing cullin-RING E3 ubiquitin ligase (CRL2) complex is an E3 ligase commonly used in targeted protein degradation (TPD). Hydroxyproline-based ligands that mimic VHL substrates have been developed as anchor molecules for proteolysis-targeting chimeras (PROTACs) in TPD. To expand the chemical space for VHL ligands, we conducted fragment screening using VHL-ELOB-ELOC (VBC) proteins.
View Article and Find Full Text PDFOutside-in engineering of cadherin endocytosis using a conformation strengthening antibody.
Nat Commun
January 2025
Biophysics Graduate Group, University of California, Davis, CA, USA.
P-cadherin, a crucial cell-cell adhesion protein which is overexpressed in numerous malignant cancers, is a popular target for drug delivery antibodies. However, molecular guidelines for engineering antibodies that can be internalized upon binding to P-cadherin are unknown. Here, we use a combination of biophysical, biochemical, and cell biological methods to demonstrate that trapping the P-cadherin extracellular region in an X-dimer adhesive conformation triggers cadherin endocytosis via an outside-in signaling mechanism.
View Article and Find Full Text PDFComprehensive computational analysis of differentially expressed miRNAs and their influence on transcriptomic signatures in prostate cancer.
Sci Rep
January 2025
Department of Pharmaceutics, College of Pharmacy, King Saud University, PO Box 2457, Riyadh, 11451, Saudi Arabia.
Prostate cancer presents a major health issue, with its progression influenced by intricate molecular factors. Notably, the interplay between miRNAs and changes in transcriptomic patterns is not fully understood. Our study seeks to bridge this knowledge gap, employing computational techniques to explore how miRNAs and transcriptomic alterations jointly regulate the development of prostate cancer.
View Article and Find Full Text PDFDifferences in Body Composition, Bone Density, and Tibial Microarchitecture in Division I Female Athletes Participating in Different Impact Loading Sports.
Calcif Tissue Int
January 2025
University of Pittsburgh, 3860 S. Water St., Pittsburgh, PA, 15203, USA.
Sport participation affects body composition and bone health, but the association between sport, body composition, and bone health in female athletes is complex. We compared areal bone mineral density (aBMD, DXA) and tibial volumetric bone mineral density (vBMD), geometry, microarchitecture, and estimated strength (HR-pQCT) in cross-country runners (n = 22), gymnasts (n = 23) and lacrosse players (n = 35), and investigated associations of total body lean mass (TBLM), team, and their interaction with tibial bone outcomes. Total body (TB), total hip (TH), femoral neck (FN), and lumbar spine (LS) aBMD were higher in gymnasts than runners (p < 0.
View Article and Find Full Text PDFChemical- and photo-activation of protein-protein thiol-ene coupling for protein profiling.
Commun Chem
January 2025
School of Chemistry, Trinity College Dublin, Dublin, Ireland.
The thiol-ene reaction between an alkene and a thiol can be exploited for selective labelling of cysteine residues in protein profiling applications. Here, we explore thiol-ene activation in systems from chemical models to complex cellular milieus, using UV, visible wavelength and redox initiators. Initial studies in chemical models required an oxygen-free environment for efficient coupling and showed very poor activation when using a redox initiator.
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