Bimodal Detection of Proteins by 129 Xe NMR and Fluorescence Spectroscopy.

A full understanding of biological phenomena involves sensitive and noninvasive detection. Herein, we report the optimization of a probe for intracellular proteins that combines the advantages of fluorescence and hyperpolarized 129 Xe NMR spectroscopy detection. The fluorescence detection part is composed of six residues containing a tetracysteine tag (-CCXXCC-) genetically incorporated into the protein of interest and of a small organic molecule, CrAsH. CrAsH becomes fluorescent if it binds to the tetracysteine tag. The part of the biosensor that enables detection by means of 129 Xe NMR spectroscopy, which is linked to the CrAsH moiety by a spacer, is based on a cryptophane core that is fully suited to reversibly host xenon. Three different peptides, containing the tetracysteine tag and four organic biosensors of different stereochemistry, are benchmarked to propose the best couple that is fully suited for the in vitro detection of proteins.

Bimodal fluorescence/129Xe NMR probe for molecular imaging and biological inhibition of EGFR in Non-Small Cell Lung Cancer.

Although Non-Small Cell Lung Cancer (NSCLC) is one of the main causes of cancer death, very little improvement has been made in the last decades regarding diagnosis and outcomes. In this study, a bimodal fluorescence/129Xe NMR probe containing a xenon host, a fluorescent moiety and a therapeutic antibody has been designed to target the Epidermal Growth Factor Receptors (EGFR) overexpressed in cancer cells. This biosensor shows high selectivity for the EGFR, and a biological activity similar to that of the antibody. It is detected with high specificity and high sensitivity (sub-nanomolar range) through hyperpolarized 129Xe NMR. This promising system should find important applications for theranostic use.

Understanding a host-guest model system through ¹²9Xe†NMR spectroscopic experiments and theoretical studies.

Gaining an understanding of the nature of host-guest interactions in supramolecular complexes involving heavy atoms is a difficult task. Described herein is a robust simulation method applied to complexes between xenon and members of a cryptophane family. The calculated chemical shift of xenon caged in a H2O2 probe, as modeled by quantum chemistry with complementary-orbital, topological, and energy-decomposition analyses, is in excellent agreement with that observed in hyperpolarized (129)Xe NMR spectra. This approach can be extended to other van der Waals complexes involving heavy atoms.

Synthesis of fluorinated cyclopropyl amino acid analogues: toward the synthesis of original fluorinated peptidomimetics.

A straightforward, easy, and practical access to various amino acid analogues (methionine, leucine, lysine, and arginine) from a unique fluorinated cyclopropane scaffold is described. Moreover, the synthesis, for the first time, of one tripeptide incorporating a fluorinated cyclopropane amino acid (FCAA) analogue is reported.

Syntheses and applications of monofluorinated cyclopropanes.

The combination of a fluorine atom and a cyclopropane ring, which both possess unique structural and chemical features, can generate new relevant building blocks for the discovery of efficient fluorinated biologically active agents. In this review, we report the different strategies to access monofluorocyclopropanes and highlight some of their attractive biological applications.

Toward the Synthesis of Fluorinated Analogues of HCV NS3/4A Serine Protease Inhibitors Using Methyl α-Amino-ß-fluoro-ß-vinylcyclopropanecarboxylate as Key Intermediate.

Synthesis of fluorocyclopropyl building blocks, which constitute the core of various therapeutic agents against the hepatitis C virus, is described. The relevant methyl α-amino-ß-fluoro-ß-vinylcyclopropanecarboxylate has been used as a key intermediate for the total synthesis of a fluorinated analogue of Simeprevir (TMC 435), a HCV NS3/4A protease inhibitor.

A straightforward and highly diastereoselective access to functionalized monofluorinated cyclopropanes via a Michael initiated ring closure reaction.

The synthesis of highly functionalized monofluorinated cyclopropanes based on a Michael Initiated Ring Closure (MIRC) reaction has been developed. The addition of quaternary ammonium salts derived from ethyl bromofluoroacetate on a panel of electron deficient alkenes followed by cyclization gave rise to an efficient access to monofluorinated cyclopropanes with good yields and remarkable diastereoselectivity.