Department of Chemistry and Biochemistry, The Ohio State University, 100 West 18th Avenue, Columbus, OH-43210, USA.
Published: November 2024
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We describe the preparation, assembly, recognition characteristics, and bioactivity of dendritic basket 6. This novel cavitand has a deep aromatic pocket with three (S)-glutamic acid dendrons at the rim to amplify water solubility and prevent self-association. H NMR spectroscopy, calorimetry (ITC), and mass spectrometry (ESI-MS) measurements validate the formation of an inclusion complex between 6 and anticancer drug methotrexate (MTX) in water (K=9.2 μM). To identify the docking pose, a comparison of computed (DFT and MM) and experimental H NMR chemical shifts suggests that MTX folds inside 6 (π⋅⋅⋅π), forming HBs with the peptidic dendrons while anchoring (C-H⋅⋅⋅π) to the aromatic pocket through its N-methyl group. In consequence, 6 selectively binds MTX in competition with structurally similar folic acid and leucovorin (reversal poisoning agent). While the host is biocompatible (HEK293; IC>150 μM) and produces inclusion complex [MTX⊂6] in cell media, it experiences limitation in pharmacokinetic sequestration of MTX as dihydrofolate reductase's affinity to the drug is suggested to prevail over that of 6. Nonetheless, considering the basket's biocompatibility, tunability, and chemoselectivity, it stands as the leading candidate in the pursuit of an effective abiotic antidote for methotrexate poisoning.
Blueberry has a diversity of anthocyanins that confer its characteristic, blue-coloured skin. Whilst most cultivars produce only anthocyanin glycosides, some can add aliphatic or aromatic groups to the sugar moiety to create acylated anthocyanins. Due to their enhanced stability, acylated anthocyanins represent an attractive breeding target in blueberry.
Natural Science Laboratory, Division of Medicinal and Pharmaceutical Chemistry, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, 700032, India.
The global outbreak of COVID-19 infection is the first pandemic the world has experienced in this 21 century. The novel coronavirus 2019 (nCoV-19) also called the SARS-CoV-2 is the reason behind the severe acute respiratory syndrome (SARS) that led to this worldwide crisis. In this current post-pandemic situation, despite having effective vaccines, the paucity of orally administrable drug molecules for such infections is a major drawback in this current scenario.
Department of Chemistry, School of Science, Westlake University, Hangzhou 310030, Zhejiang Province, China; Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou 310024, Zhejiang Province, China; Institute of Natural Sciences, Westlake Institute for Advanced Study, Hangzhou 310024, Zhejiang Province, China. Electronic address:
Arginine methylation is an important posttranslational modification that regulates epigenetics and pre-mRNA splicing. Similar to lysine methylation, reader proteins that bind site-specific modified proteins are key mediators for arginine methylation functions. Some arginine methylation has been shown significant functions from phenotype, but the molecular mechanisms remain elusive, probably due to lack of identification of the readers.
ARC Centre of Excellence for Innovations in Peptide & Protein Science, Research School of Chemistry, Australian National University, Canberra, ACT 2601, Australia.
Cyanotryptophans (CN-Trp) are privileged multimodal reporters on protein structure. They are similar in size to the canonical amino acid tryptophan and some of them exhibit bright fluorescence which responds sensitively to changes in the environment. We selected aminoacyl-tRNA synthetases specific for 4-, 5-, 6-, and 7-CN-Trp for high-yield in vivo production of proteins with a single, site-specifically introduced nitrile label.
State Key Laboratory of Chemical Biology, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200032, China.
Halogenases are spurring a growing interest in the fields of biosynthesis and biocatalysis. Although various halogenases have been identified in numerous natural product biosynthetic pathways, the mechanisms for multiple halogenations and site-selectivity remain largely unclear. In this study, we biochemically characterized FasV, a flavin-dependent halogenase (FDH) that catalyzes five successive chlorinations in the biosynthesis of the naphthacene-containing aromatic polyketide naphthacemycin.
