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Facile preparation of sulfonium peptide and protein probes for selective crosslinking of methyllysine readers.
Chem Sci
December 2024
Department of Chemistry, School of Science, Westlake University 310030 Hangzhou Zhejiang Province China.
Sulfonium is an electrophilic and biocompatible group that is widely applied in synthetic chemistry on small molecules. However, there have been few developments of peptide or protein-based sulfonium tools. We recently reported sulfonium-mediated tryptophan crosslinking and developed NleSme2 (norleucine-dimethylsulfonium) peptides as dimethyllysine mimics that crosslink site-specific methyllysine readers.
View Article and Find Full Text PDFPathophysiology-Directed Engineering of a Combination Nanoanalgesic for Neuropathic Pain.
Adv Sci (Weinh)
December 2024
Department of Pharmaceutics, College of Pharmacy, Third Military Medical University (Army Medical University), Chongqing, 400038, P. R. China.
Neuropathic pain, one of the most refractory pain diseases, remains a formidable medical challenge. There is still an unmet demand for effective and safe therapies to address this condition. Herein, a rat model of nerve injury-induced neuropathic pain is first established to explore its pathophysiological characteristics.
View Article and Find Full Text PDFIn Vitro and In Vivo Comparison of Random versus Site-Specific Conjugation of Bifunctional Chelating Agents to the CD33-Binding Antibody for Use in Alpha- and Beta-Radioimmunotherapy.
ACS Omega
December 2024
College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, Saskatchewan S7N 5E5, Canada.
Radiometal chelator conjugation is a cornerstone of radioimmunotherapy (RIT). Continued interest in selective placement of chelators remains an active topic of discussion in the field. With several simple site-specific methods being recently reported, it was of interest to investigate the benefits and potential drawbacks of the site-specific method with a full comparison to a more typical random conjugation method that is currently utilized in clinical applications.
View Article and Find Full Text PDFInvestigating protein degradability through site-specific ubiquitin ligase recruitment.
RSC Chem Biol
December 2024
Department of Chemistry, University of Pittsburgh Pittsburgh PA 15260 USA
We report targeted protein degradation through the site-specific recruitment of native ubiquitin ligases to a protein of interest conjugation of E3 ligase ligands. Direct comparison of degradation ability of proteins displaying the corresponding bioconjugation handle at different regions of protein surfaces was explored. We demonstrate the benefit of proximal lysine residues and investigate flexibility in linker length for the design of optimal degraders.
View Article and Find Full Text PDFMitigating genetic instability caused by the excision activity of the C31 integrase in .
Appl Environ Microbiol
December 2024
MOE Key Laboratory of Industrial Fermentation Microbiology, College of Biotechnology, Tianjin University of Science and Technology, Tianjin, China.
Over the past three decades, the integrase (Int) from phage C31 has become a valuable genome engineering tool across various species. C31 Int was thought to mediate unidirectional site-specific integration ( × to and ) in the absence of the phage-encoded recombination directionality factor (RDF). However, we have shown in this study that Int can also catalyze reverse excision ( × to and ) at low frequencies in and , causing genetic instability in engineered strains.
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