The linkage of two identical binding motifs by a molecular photoswitch has proven to be a straightforward and versatile strategy to control substrate binding affinity by light. Stimulus control of binding properties in artificial receptors is partly inspired by the dynamic behavior of proteins and is highly attractive as it could, for example, improve extraction processes and allow (de)activation of membrane transport on demand. This feature article summarizes the development and design principles of molecular tweezers containing a molecular photoswitch as the core unit. Besides the control of binding affinity by isomerization, the effect of substrate binding on the isomerization behavior is discussed where data is available. While the latter often receives less attention, it could be of benefit in the future creation of multi-stimuli-controlled molecular switching and machine-like systems.
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http://dx.doi.org/10.1039/d2cc04329g | DOI Listing |
Sci Adv
January 2025
Center for Microbiome Research of Med-X Institute, Shaanxi Provincial Key Laboratory of Sepsis in Critical Care Medicine, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an 710061, China.
The rare metal element molybdenum functions as a cofactor in molybdoenzymes that are essential to life in almost all living things. Molybdate can be captured by the periplasmic substrate-binding protein ModA of ModABC transport system in bacteria. We demonstrate that ModA plays crucial roles in growth, multiple metabolic pathways, and ROS tolerance in .
View Article and Find Full Text PDFPLoS One
January 2025
Department of Biochemistry, Memorial University of Newfoundland, St. John's, Newfoundland and Labrador, Canada.
Geranylgeranyl pyrophosphate synthase (GGPPS), a key enzyme in protein prenylation, plays a critical role in cellular signal transduction and is a promising target for cancer therapy. However, the enzyme's native hexameric quaternary structure presents challenges for crystallographic studies. The primary objective of this study was to engineer dimeric forms of human GGPPS to facilitate high-resolution crystallographic analysis of its ligand binding interactions.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
College of Chemistry, State Key Laboratory of Elemento-Organic Chemistry, Key Laboratory of Functional Polymer Materials (Ministry of Education), Frontiers Science Center for New Organic Matter, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University, Tianjin 300071, China.
On the one hand, nature utilizes hierarchical assemblies to create complex biological binding pockets, enabling ultrastrong recognition toward substrates in aqueous solutions. On the other hand, chemists have been fervently pursuing high-affinity recognition by constructing covalently well-preorganized stereoelectronic cavities. The potential of noncovalent assembly, however, for enhancing molecular recognition has long been underestimated.
View Article and Find Full Text PDFJ Med Chem
January 2025
Institute of Pharmacy, Pharmaceutical/Medicinal Chemistry and Tübingen Center for Academic Drug Discovery, Eberhard Karls University Tübingen, Auf der Morgenstelle 8, 72076 Tübingen, Germany.
The main protease (M) of SARS-CoV-2 is a key drug target for the development of antiviral therapeutics. Here, we designed and synthesized a series of small-molecule peptidomimetics with various cysteine-reactive electrophiles. Several compounds were identified as potent SARS-CoV-2 M inhibitors, including compounds (IC = 0.
View Article and Find Full Text PDFArch Microbiol
January 2025
Department of Biological Sciences, Birla Institute of Technology and Science, Pilani, K K Birla Goa Campus, NH17B, Zuarinagar, Goa, 403726, India.
The gene gp13 in bacteriophage Phi11 has been annotated as a Single-Stranded DNA binding protein (SSB protein, GenBank accession no. NC_004615.1).
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