ABSTRACT
Comprehensive single-cell metabolic profiling is critical for revealing phenotypic heterogeneity and elucidating the molecular mechanisms underlying biological processes. However, single-cell metabolomics remains challenging because of the limited metabolite coverage and inability to discriminate isomers. Herein, we establish a single-cell metabolomics platform for in-depth organic mass cytometry. Extended single-cell analysis time guarantees sufficient MS/MS acquisition for metabolite identification and the isomers discrimination while online sampling ensures the high-throughput of the method. The largest number of identified metabolites (approximately 600) are achieved in single cells and fine subtyping of MCF-7 cells is first demonstrated by an investigation on the differential levels of 3-hydroxybutanoic acid among clusters. Single-cell transcriptome analysis reveals differences in the expression of 3-hydroxybutanoic acid downstream antioxidative stress genes, such as metallothionein 2 (MT2A), while a fluorescence-activated cell sorting assay confirms the positive relationship between 3-hydroxybutanoic acid and target proteins; these results suggest that the heterogeneity of 3-hydroxybutanoic acid provides cancer cells with different ability to resist surrounding oxidative stress. Our method paves the way for deep single-cell metabolome profiling and investigations on the physiological and pathological processes that occur during cancer.
Subject(s)
Metabolomics , Single-Cell Analysis , Humans , Single-Cell Analysis/methods , Metabolomics/methods , MCF-7 Cells , Metabolome , Tandem Mass Spectrometry/methods , Flow Cytometry/methods , Hydroxybutyrates/metabolism , Oxidative Stress , Gene Expression Profiling/methodsABSTRACT
We report supramolecular helical assembly in water of ß-turn structured bis(N-amidothioureas) containing Br-substitutes of moderate halogen bonding ability, promoted by stronger hydrophobic interaction. The helical polymers show an unusual negative nonlinear CD-ee dependence.
ABSTRACT
A C-terminal amidothiourea motif is shown to promote a ß-turn-like folded conformation in a series of ß-amino acid-based short peptides in both the solid state and solution phase by an intramolecular 11-membered ring hydrogen bond.