Click-and-Release Formation of Urea Bonds in Living Cells Enabled by Micelle Nanoreactors.

The development of innovative strategies enabling chemical reactions in living systems is of great interest for exploring and manipulating biological processes. Herein, we present a pioneering approach based on both bioorthogonal and confined chemistry for intracellular drug synthesis. Exploiting a click-to-release reaction, we engineered nanoparticles capable of synthesizing drugs within cellular environments through bioorthogonal reactions with cyclooctynes.

Formation of extraterrestrial peptides and their derivatives.

The formation of protein precursors, due to the condensation of atomic carbon under the low-temperature conditions of the molecular phases of the interstellar medium, opens alternative pathways for the origin of life. We perform peptide synthesis under conditions prevailing in space and provide a comprehensive analytic characterization of its products. The application of C allowed us to confirm the suggested pathway of peptide formation that proceeds due to the polymerization of aminoketene molecules that are formed in the C + CO + NH reaction.

Ultrasound assisted extraction of amino acids and nucleobases from clay minerals and astrobiological samples.

The study of organic molecules in meteorite and return samples allows for the understanding of the chemistry that undergoes in our Solar System. The present work aims at studying ultrasound assisted extraction technique as effective extraction method for these molecules in extraterrestrial samples and analogs. Optimal conditions were selected from the investigation of ultrasonic frequency, irradiation duration and solvent effects on amino acids, nucleobases and dipeptides extraction yields from a model clay-rich mineral matrix.

Combination of Targeted Therapies for Colorectal Cancer Treatment.

The design of innovative therapeutic strategies enabling the selective destruction of tumor cells while sparing healthy tissues remains highly challenging in cancer therapy. Here, we show that the combination of two targeted therapies, including bevacizumab (), and a β-glucuronidase-responsive albumin-binding prodrug of monomethyl auristatin E (), is efficient for the treatment of colorectal cancer implanted in mice. This combined therapy produces a therapeutic activity superior to that of the association of and currently used to treat patients with this pathology.

VOC-Based Probes, a New Set of Analytical Tools to Monitor Patient Health from Blood Sample. Proof of Concept on Tracking COVID-19 Infection.

Induced volatolomics is an emerging field that holds promise for many biomedical applications including disease detection and prognosis. In this pilot study, we report the first use of a cocktail of volatile organic compounds (VOCs)-based probes to highlight new metabolic markers allowing disease prognosis. In this pilot study, we specifically targeted a set of circulating glycosidases whose activities could be associated with critical COVID-19 illness.

Induced-volatolomics for the design of tumour activated therapy.

The discovery of tumour-associated markers is of major interest for the development of selective cancer chemotherapy. Within this framework, we introduced the concept of induced-volatolomics enabling to monitor simultaneously the dysregulation of several tumour-associated enzymes in living mice or biopsies. This approach relies on the use of a cocktail of volatile organic compound (VOC)-based probes that are activated enzymatically for releasing the corresponding VOCs.

Traceless Staudinger Ligation to Access Stable Aminoacyl- or Peptidyl-Dinucleotide.

Aminoacyl- and peptidyl-tRNA are specific biomolecules involved in many biological processes, from ribosomal protein synthesis to the synthesis of peptidoglycan precursors. Here, we report a post-synthetic approach based on traceless Staudinger ligation for the synthesis of a stable amide bond to access aminoacyl- or peptidyl-di-nucleotide. A series of amino-acid and peptide ester phenyl phosphines were synthetized, and their reactivity was studied on a 2'-N di-nucleotide.

Stimuli-Responsive Catenane-Based Catalysts.

Rotaxanes and molecular knots exhibit particular properties resulting from the presence of a mechanical bond within their structure that maintains the molecular components interlocked in a permanent manner. On the other hand, the disassembly of the interlocked architecture through the breakdown of the mechanical bond can activate properties which are masked in the parent compound. Herein, we present the development of stimuli-responsive Cu -complexed [2]catenanes as OFF/ON catalysts for the copper-catalyzed alkyne-azide cycloaddition (CuAAC) reaction.

A β-Cyclodextrin-Albumin Conjugate for Enhancing Therapeutic Efficacy of Cytotoxic Drugs.

Enhancing the selectivity of anticancer drugs currently used in the clinic is of great interest in order to propose more efficient chemotherapies with fewer side effects for patients. In this context, we developed a β-cyclodextrin trimer that binds to circulating albumin to form the corresponding bioconjugate in the bloodstream. This latter can then entrap doxorubicin following its i.

Focused ultrasound extraction versus microwave-assisted extraction for extraterrestrial objects analysis.

Search for organic bioindicators in the solar system is a fundamental challenge for the space research community. If tremendous improvements have been achieved in detection, little or no research has been dedicated to extraction of the targets from the studied mineral matrices. Apart from thermodesorption, no extraction step was ever performed in situ within the context of biomarker detection experiments.

Integrative analytical workflow to enhance comprehensive analysis of organic molecules in extraterrestrial objects.

Molecular identification is a fundamental issue in astrobiology to investigate the routes of emergence of life on our planet involving in particular a potential seeding of extraterrestrial organic matter on the primitive Earth. However, this project encompasses major difficulties due to the low concentration of molecules present in bodies of the Solar System. This work proposes an integrative analytical workflow, no longer based on GC-MS instruments, to enhance comprehensive analysis of organic markers in these objects.

Induced volatolomics of pathologies.

Volatolomics allows us to elucidate cell metabolic processes in real time. In particular, a volatile organic compound (VOC) excreted from our bodies may be specific for a certain disease, such that measuring this VOC may afford a simple, fast, accessible and safe diagnostic approach. Yet, finding the optimal endogenous volatile marker specific to a pathology is non-trivial because of interlaboratory disparities in sample preparation and analysis, as well as high interindividual variability.

A Novel Proteomics-Based Strategy for the Investigation of Peptide Sequences in Extraterrestrial Samples.

Method development is one of the objectives of the astrophysical community for characterizing the organic matter in objects of the solar system. In this context, we report on the development of an enzyme-catalyzed stereoselective hydrolysis, inspired by the proteomics discipline, which has enabled the indirect detection of peptide sequences in extraterrestrial samples. A proof of concept has been performed on a Murchison extract.

Phosphine-Mediated Bioconjugation of the 3'-End of RNA.

Staudinger ligation is an attractive bio-orthogonal reaction that has been widely used to tag proteins, carbohydrates, and nucleic acids. Here, we explore the traceless variant of the Staudinger ligation for 3'-end modification of oligoribonucleotides. An azido-containing dinucleotide was used to study the ligation.

In vivo synthesis of triple-loaded albumin conjugate for efficient targeted cancer chemotherapy.

The development of selective anticancer drugs avoiding side effects met in the course of almost all current treatments is of major interest for cancer patients. Here, we report on a novel β-glucuronidase-responsive drug delivery system allowing the in vivo synthesis of triple-loaded albumin conjugate. Following intravenous administration, the glucuronide prodrug reacts in the blood stream with the cysteine-34 residue of circulating albumin through thio-Michael addition, enabling the bioconjugation of three Monomethylauristatin E (MMAE) molecules to the plasmatic protein.

Volatile Organic Compound Based Probe for Induced Volatolomics of Cancers.

The development of efficient protocols for cancer diagnosis remains highly challenging. An emerging approach relies on the detection in exhaled breath of volatile organic compounds (VOC) produced by tumours. In this context, described here is a novel strategy in which a VOC-based probe is converted selectively in malignant tissues, by a tumour-associated enzyme, for releasing the corresponding VOC.

Data-Driven UPLC-Orbitrap MS Analysis in Astrochemistry.

Meteorites have been found to be rich and highly diverse in organic compounds. Next to previous direct infusion high resolution mass spectrometry experiments (DI-HR-MS), we present here data-driven strategies to evaluate UPLC-Orbitrap MS analyses. This allows a comprehensive mining of structural isomers extending the level of information on the molecular diversity in astrochemical materials.

Primary Step Towards In Situ Detection of Chemical Biomarkers in the UNIVERSE via Liquid-Based Analytical System: Development of an Automated Online Trapping/Liquid Chromatography System.

The search for biomarkers in our solar system is a fundamental challenge for the space research community. It encompasses major difficulties linked to their very low concentration levels, their ambiguous origins (biotic or abiotic), as well as their diversity and complexity. Even if, in 40 years' time, great improvements in sample pre-treatment, chromatographic separation and mass spectrometry detection have been achieved, there is still a need for new in situ scientific instrumentation.

Controlled Release of a Micelle Payload via Sequential Enzymatic and Bioorthogonal Reactions in Living Systems.

A bioorthogonal approach is explored to release the content of nanoparticles on demand. Exploiting our recently described click-and-release technology, we developed a new generation of cleavable micelles able to disassemble through a sequential enzymatic and bioorthogonal activation process. Proof-of-concept experiments showed that this new approach could be successfully used to deliver the substances encapsulated into micelles in living cells as well as in mice by two complementary targeted strategies.

A β-glucuronidase-responsive albumin-binding prodrug programmed for the double release of monomethyl auristatin E.

We report on the synthesis, and biological evaluations of a dimeric β-glucuronidase-responsive albumin-binding prodrug designed for the double release of MMAE upon a single enzymatic activation step. This prodrug produced a significant antitumour activity in mice bearing subcutaneous LS174T colorectal adenocarcinoma xenografts without inducing side effects.

TCA precipitation and ethanol/HCl single-step purification evaluation: One-dimensional gel electrophoresis, bradford assays, spectrofluorometry and Raman spectroscopy data on HSA, Rnase, lysozyme - Mascots and Skyline data.

The data presented here are related to the research paper entitled "Study of a Novel Agent for TCA Precipitated Proteins Washing - Comprehensive Insights into the Role of Ethanol/HCl on Molten Globule State by Multi-Spectroscopic Analyses" (Eddhif et al., submitted for publication) [1]. The suitability of ethanol/HCl for the washing of TCA-precipitated proteins was first investigated on standard solution of HSA, cellulase, ribonuclease and lysozyme.

Development of liquid chromatography high resolution mass spectrometry strategies for the screening of complex organic matter: Application to astrophysical simulated materials.

The present work aims at developing two LC-HRMS setups for the screening of organic matter in astrophysical samples. Their analytical development has been demonstrated on a 100-µg residue coming from the photo-thermo chemical processing of a cometary ice analog produced in laboratory. The first 1D-LC-HRMS setup combines a serially coupled columns configuration with HRMS detection.

Study of a novel agent for TCA precipitated proteins washing - comprehensive insights into the role of ethanol/HCl on molten globule state by multi-spectroscopic analyses.

Unlabelled: Sample preparation for mass spectrometry-based proteomics is a key step for ensuring reliable data. In gel-free experimental workflows, protein purification often starts with a precipitation stage using trichloroacetic acid (TCA). In presence of TCA, proteins precipitate in a stable molten globule state making the pellet difficult to solubilize in aqueous buffer for proteolytic digestion and MS analysis.

Polycyclic aromatic hydrocarbons in fruits and vegetables: Origin, analysis, and occurrence.

Feed intake, for non-smokers, is the first route of contamination to polycyclic aromatic hydrocarbons (PAHs), which are potentially toxic compounds via ingestion. Investigations are focused on the presence of PAHs in fruits and vegetables. Transfer of PAHs can occur from air and soil during cultivation.

Development and evaluation of β-galactosidase-sensitive antibody-drug conjugates.

The selective destruction of tumour cells while sparing healthy tissues is one of the main challenges in cancer therapy. Antibody-drug conjugates (ADCs) are arguably the most rapidly expanding class of targeted cancer therapies. Efficient drug conjugation and release technologies are essential for the development of these new therapeutic agents.