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A method for isolation and identification of 21 glues from cadavers has been developed. Chromogenic reactions are proposed to be used for identification and conditions of chromatography in a thin layer of sorbent developed.
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RSC Med Chem
February 2025
Laboratory of Chemical Biology, Department of Biomedical Engineering and Institute for Complex Molecular Systems, Eindhoven University of Technology Groene Loper 3 5612 AE Eindhoven The Netherlands
Protein-protein interactions (PPIs) are key regulators of various cellular processes. Modulating PPIs with small molecules has gained increasing attention in drug discovery, particularly targeting the 14-3-3 protein family, which interacts with several hundred client proteins and plays a central role in cellular networks. However, targeting a specific PPI of the hub protein 14-3-3, with its plethora of potential client proteins, poses a significant selectivity challenge.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
March 2025
Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
For decades, microtubules-composed of αβ-tubulin dimers-have been primary targets for cancer chemotherapy. While eight binding sites on the tubulin dimer have been structurally characterized, this study reveals a ninth. We found that the tubulin inhibitor Tumabulin-1 (TM1, a BML284 derivative) binds simultaneously to the well-known colchicine site and a previously unknown site, designated as Tumabulin site.
View Article and Find Full Text PDFRSC Chem Biol
March 2025
Novartis Biomedical Research Fabrikstrasse 2 CH-4056 Basel Switzerland
Many disease-relevant and functionally well-validated targets are difficult to drug. Their poorly defined 3D structure without deep hydrophobic pockets makes the development of ligands with low molecular weight and high affinity almost impossible. For these targets, incorporation into a ternary complex may be a viable alternative to modulate and in most cases inhibit their function.
View Article and Find Full Text PDFSci Adv
March 2025
Department of Ophthalmology, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200011, China.
Topical drug delivery on ocular surface always suffers from frequent administration and low bioavailability due to short drug residence. Despite advances of different adhesive ophthalmic drugs in extending release, cornea and eyelid nonselective adhesion inevitably causes ocular discomfort and even damage. Here, we describe in situ formation of an adhesive lubricative Janus nanocoating (ALJN) to enable long-lasting comfort drug delivery.
View Article and Find Full Text PDFCell Commun Signal
February 2025
Center for Cooperative Research in Biosciences (CIC Biogune), Basque Research and Technology Alliance (BRTA), 48160, Derio, Spain.
Background: The specificity of the ubiquitination process is mediated by the E3 ligases. Discriminating genuine substrates of E3s from mere interacting proteins is one of the major challenges in the field. We previously developed BioE3, a biotin-based approach that uses BirA-E3 fusions together with ubiquitin fused to a low-affinity AviTag to obtain a site-specific and proximity-dependent biotinylation of the substrates.
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