Probing lysine mono-methylation in histone H3 tail peptides with an abiotic receptor coupled to a non-plasmonic resonator.

Binder and effector molecules that allow studying and manipulating epigenetic processes are of biological relevance and pose severe technical challenges. We report the first example of a synthetic receptor able to recognize mono-methylated lysines in a histone H3 tail peptide, which has relevant functions in epigenetic regulation. Recognition is robust and specific regardless of the position and the number of mono-methylated lysines along the polypeptide chain. The peptide is first captured in solution by a tetraphosphonate cavitand (Tiiii) that selectively binds its Lys-NMe+ moieties. Separation from solution and detection of the peptide-Tiiii complexes is then enabled in one single step by an all dielectric SiO2-TiO2 core-shell resonator (T-rex), which captures the complex and operates fully reproducible signal transduction by non-plasmonic surface enhanced Raman scattering (SERS) without degrading the complex. The realized abiotic probe is able to distinguish multiple mono-methylated peptides from the single mono-methylated ones.

[1]  D. Reinhoudt,et al.  Multivalency in supramolecular chemistry and nanofabrication. , 2004, Organic & biomolecular chemistry.

[2]  Ivano Alessandri,et al.  Enhancing Raman scattering without plasmons: unprecedented sensitivity achieved by TiO2 shell-based resonators. , 2013, Journal of the American Chemical Society.

[3]  B. Garcia,et al.  Quantitative proteomic analysis of histone modifications. , 2015, Chemical reviews.

[4]  Bo Liedberg,et al.  Differential Protein Assembly on Micropatterned Surfaces with Tailored Molecular and Surface Multivalency , 2006, Chembiochem : a European journal of chemical biology.

[5]  E. Dalcanale,et al.  Cavitands Endow All-Dielectric Beads With Selectivity for Plasmon-Free Enhanced Raman Detection of Nε-Methylated Lysine. , 2016, ACS applied materials & interfaces.

[6]  C. Allis,et al.  Methylation of histone H3 at lysine 4 is highly conserved and correlates with transcriptionally active nuclei in Tetrahymena. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[7]  E. Dalcanale,et al.  Supramolecular sensing with phosphonate cavitands. , 2013, Accounts of chemical research.

[8]  Z. Azizi,et al.  Indicator displacement assays inside live cells. , 2015, Angewandte Chemie.

[9]  Ivano Alessandri,et al.  All-oxide Raman-active traps for light and matter: probing redox homeostasis model reactions in aqueous environment. , 2014, Small.

[10]  D. Figeys,et al.  The functional diversity of protein lysine methylation , 2014, Molecular systems biology.

[11]  D. Macartney,et al.  Selective molecular recognition of methylated lysines and arginines by cucurbit[6]uril and cucurbit[7]uril in aqueous solution. , 2013, Organic & biomolecular chemistry.

[12]  Kevin D. Daze,et al.  A Simple Calixarene Recognizes Post‐translationally Methylated Lysine , 2009, Chembiochem : a European journal of chemical biology.

[13]  Sean D. Taverna,et al.  How chromatin-binding modules interpret histone modifications: lessons from professional pocket pickers , 2007, Nature Structural &Molecular Biology.

[14]  P. Trojer,et al.  Targeting histone lysine methylation in cancer. , 2015, Pharmacology & therapeutics.

[15]  Juntao Li,et al.  Histone H3 lysine 4 monomethylation (H3K4me1) and H3 lysine 9 monomethylation (H3K9me1): distribution and their association in regulating gene expression under hyperglycaemic/hyperinsulinemic conditions in 3T3 cells. , 2012, Biochimie.

[16]  J. Lyons,et al.  Structural study of a small molecule receptor bound to dimethyllysine in lysozyme , 2014, Chemical science.

[17]  P. B. Crowley,et al.  Protein Camouflage: Supramolecular Anion Recognition by Ubiquitin , 2016, Chembiochem : a European journal of chemical biology.

[18]  Paolo Bergese,et al.  Nanomechanical recognition of N-methylammonium salts. , 2012, Journal of the American Chemical Society.

[19]  Jurriaan Huskens,et al.  A model for describing the thermodynamics of multivalent host-guest interactions at interfaces. , 2004, Journal of the American Chemical Society.

[20]  C. Ottmann,et al.  Molecular tweezers modulate 14-3-3 protein-protein interactions. , 2013, Nature chemistry.

[21]  Wenwan Zhong,et al.  Self-Aggregating Deep Cavitand Acts as a Fluorescence Displacement Sensor for Lysine Methylation. , 2016, Journal of the American Chemical Society.

[22]  D. Dougherty.  The cation-π interaction. , 2013, Accounts of chemical research.

[23]  Michele Suman,et al.  Cavitands at Work: From Molecular Recognition to Supramolecular Sensors , 2004 .

[24]  Kevin D. Daze,et al.  The cation-π interaction at protein-protein interaction interfaces: developing and learning from synthetic mimics of proteins that bind methylated lysines. , 2013, Accounts of chemical research.

[25]  Ivano Alessandri,et al.  Enhanced Raman Scattering with Dielectrics. , 2016, Chemical reviews.

[26]  Scott M. Carlson,et al.  Emerging technologies to map the protein methylome. , 2014, Journal of molecular biology.

[27]  E. Dalcanale,et al.  The Origin of Selectivity in the Complexation of N-Methyl Amino Acids by Tetraphosphonate Cavitands. , 2016, Journal of the American Chemical Society.

[28]  Kevin D. Daze,et al.  Antibody-free reading of the histone code using a simple chemical sensor array. , 2012, Journal of the American Chemical Society.

[29]  E. Dalcanale,et al.  Fully reversible guest exchange in tetraphosphonate cavitand complexes probed by fluorescence spectroscopy. , 2008, Chemical communications.

[30]  Costantino De Angelis,et al.  Plasmon-free SERS detection of environmental CO2 on TiO2 surfaces. , 2016, Nanoscale.

[31]  S. Jacobs,et al.  Structure of HP1 Chromodomain Bound to a Lysine 9-Methylated Histone H3 Tail , 2002, Science.

[32]  A. Jeltsch,et al.  A fluorescence-based supramolecular tandem assay for monitoring lysine methyltransferase activity in homogeneous solution. , 2012, Chemistry.

[33]  Matthew E. Cuellar,et al.  A small molecule receptor that selectively recognizes trimethyl lysine in a histone peptide with native protein-like affinity. , 2010, Chemical communications.

[34]  W. Nau,et al.  Dynamically analyte-responsive macrocyclic host-fluorophore systems. , 2014, Accounts of chemical research.