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Diverse mechanisms have been described for selective enrichment of biomolecules in membrane-bound organelles, but less is known about mechanisms by which molecules are selectively incorporated into biomolecular assemblies such as condensates that lack surrounding membranes. The chemical environments within condensates may differ from those outside these bodies, and if these differed among various types of condensate, then the different solvation environments would provide a mechanism for selective distribution among these intracellular bodies. Here we use small molecule probes to show that different condensates have distinct chemical solvating properties and that selective partitioning of probes in condensates can be predicted with deep learning approaches. Our results demonstrate that different condensates harbor distinct chemical environments that influence the distribution of molecules, show that clues to condensate chemical grammar can be ascertained by machine learning and suggest approaches to facilitate development of small molecule therapeutics with optimal subcellular distribution and therapeutic benefit.
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http://dx.doi.org/10.1038/s41589-023-01432-0 | DOI Listing |
Angew Chem Int Ed Engl
December 2024
Zhengzhou University, College of Chemistry, and Pingyuan Laboratory, CHINA.
Transition-metal-regulated radical cross coupling enables the selective bonding of two distinct transient radicals, whereas the catalytic method for sorting two almost identical transient radicals, especially similar benzyl radicals, is still rare. Herein, we show that leveraging dual photoredox/cobalt catalysis can selectively couple two similar benzyl radicals. Using easily accessible methylarenes and phenylacetates (benzyl N-hydroxyphthalimide (NHPI) esters) as benzyl radical sources, a range of unsymmetrical 1,2-diarylethane classes via the 1°-1°, 1°-2°, 1°-3°, 2°-2°, 2°-3° and 3°-3° couplings were obtained with broad functional group tolerance.
View Article and Find Full Text PDFMol Pharm
December 2024
Pharmaceutical Technology and Biopharmaceutics, Department of Pharmacy, Ludwig-Maximilians-Universität München, Butenandtstrasse 5-13, 81377 Munich, Germany.
There is still an insufficient understanding of how the characteristics of protein drugs are maintained in the solid state of lyophilizates, including aspects such as protein distances, local environment, and structural preservation. To this end, we evaluated protein folding and the molecules' nearest environment by electron paramagnetic resonance (EPR) spectroscopy. Double electron-electron resonance (DEER) probe distances of up to approximately 200 Å and is suitable to investigate protein folding, local concentration, and aggregation, whereas electron spin echo envelope modulation (ESEEM) allows the study of the near environment within approximately 10 Å of the spin label.
View Article and Find Full Text PDFDalton Trans
December 2024
Department of Chemistry, Birla Institute of Technology and Science Pilani, Hyderabad, Telangana-500078, India.
This article describes an optically adjustable, dual complementary molecular TRANSFER and COMPLEMENT logic gate as well as an extremely rare design of excitation-modulated logic systems using a pyrene coupled bis(indolyl)methane derivative (1) in Brij-58 micelles, triggered by different chemical stimuli. We have looked into the optical response of the probe molecule towards variety of analytes, including OH, CN, Hg, EDTA ., at various excitation channels, in order to achieve this goal.
View Article and Find Full Text PDFChem Commun (Camb)
December 2024
School of Chemistry and Chemical Engineering, Nanchang University, Nanchang 330031, China.
Using temperature modulation, two distinct hydrogen bond organic frameworks HOF-C and HOF-K with different pore sizes were synthesized from the same ligands, tris(4-(4-1,2,4-triazole-4-yl)phenyl)amine. The pore size difference prevents TRZ from entering HOF-K, while allowing TRZ to selectively insert into the larger-pored HOF-C to form HOF-C-TRZ. The donor-acceptor (D-A) structure formed in HOF-C-TRZ enhances its photoelectric response and exhibits exceptional uranium reduction under visible light irradiation.
View Article and Find Full Text PDFJ Chromatogr A
December 2024
Department of Biochemical Engineering, School of Chemical Engineering and Technology and Key Laboratory of Systems Bioengineering and Frontiers Science Center for Synthetic Biology (Ministry of Education), Tianjin University, Tianjin 300350, PR China. Electronic address:
Our previous studies on protein adsorption onto anion-exchangers of poly(ethylenimine) (PEI)-grafted Sepharose FF (PEI-Sepharose) proved their significantly improved performance over the commercial nongrafting anion-exchangers such as Q Sepharose FF, and it was found the protein adsorption behavior on PEI-Sepharose was more sensitive to counterions (Cl, SCN, HPO and SO). However, the complicated role of counterions has not been well interpreted due to their distinct chemical and physical characteristics. Thus, we have further studied the counterion effects by adding two halide ions (F and Br) to explore the effects of the three halide ions on bovine serum albumin adsorption and the results were compared with previous data.
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