We describe the design and synthesis of a non-peptidic β-strand mimetic composed of alternating aryl and imidazolidin-2-one rings that can be adapted to display diverse side-chains. Solid- and solution-phase data together with calculations suggest that the desired conformation for side-chain mimicry is readily accessible and well-populated.
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http://dx.doi.org/10.1039/c2cc34791a | DOI Listing |
RSC Chem Biol
December 2024
Enamine Ltd 78 Winston Churchill Street Kyiv 02094 Ukraine +380 67 656-4026 https://www.enamine.net.
Sortase A-mediated ligation (SML) or "sortagging" has become a popular technology to selectively introduce structurally diverse protein modifications. Despite the great progress in the optimization of the reaction conditions and design of miscellaneous C- or N-terminal protein modification strategies, the reported yields of conjugates are highly variable. In this study, we have systematically investigated C-terminal protein sortagging efficiency using a combination of several rationally selected and modified acceptor proteins and a panel of incoming surrogate non-peptidic amine nucleophile substrates varying in the structural features of their amino linker parts and cargo molecules.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
January 2025
Darmstadt University of Technology: Technische Universitat Darmstadt, Clemens-Schöpf-Institute of Organic Chemistry and Biochemistry, Alarich-Weiss-Strasse 4, 64287, Darmstadt, GERMANY.
J Med Chem
January 2025
Department of Biochemistry and Molecular Biomedicine, Faculty of Biology, Institute of Biomedicine of the University of Barcelona (IBUB), University of Barcelona, Barcelona 08028, Spain.
Activation of cannabinoid CB receptors (CBR) by agonists induces analgesia but also induces cognitive impairment through the heteromer formed between CBR and the serotonin 5HT receptor (5HTR). This side effect poses a serious drawback in the therapeutic use of cannabis for pain alleviation. Peptides designed from the transmembrane helices of CBR, which are predicted to bind 5HTR and alter the stability of the CBR-5HTR heteromer, have been shown to avert CBR agonist-induced cognitive impairment while preserving analgesia.
View Article and Find Full Text PDFCell Rep
November 2024
Department of Biochemistry & Biophysics, Texas A&M University, College Station, TX 77840, USA. Electronic address:
Safe, effective, and low-cost oral antiviral therapies are needed to treat those at high risk for developing severe COVID-19. To that end, we performed a high-throughput screen to identify non-peptidic, non-covalent inhibitors of the SARS-CoV-2 main protease (Mpro), an essential enzyme in viral replication. NZ-804 was developed from a screening hit through iterative rounds of structure-guided medicinal chemistry.
View Article and Find Full Text PDFJ Nephrol
October 2024
Renal Division, Department of Health Sciences, University of Milan, Milan, Italy.
Secondary hyperparathyroidism is one of the most frequent metabolic abnormalities found in patients with chronic kidney disease. The calcium-sensing receptor senses extracellular calcium and is the principal regulator of parathyroid hormone secretion. Cloning of the calcium-sensing receptor led to the development of calcimimetics, drugs that decrease parathyroid hormone secretion through the positive allosteric modulation of this receptor.
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