Résumé
Biomarker discovery is of strategic importance in health sciences, particularly in -omics approaches. However, detecting and identifying specific peptides and proteins involved in biological processes faces challenges considering their dynamic complexity. In this context, mass spectrometry represents a powerful tool and of strategic importance, paving the way for understanding of pathological processes and aiding diagnosis.However, many relevant biomarkers remain difficult to detect due to diverse factors such as low abundance, ionization potential, complex localization, or lack of specificity. Directly analyzing complex biological samples without processing is essential. MALDI-MS technology addresses these challenges, offering a suitable technique for biomolecule analysis.Alongside conventional chemical reactions, new approaches aim to enhance labeling selectivity process, including the introduction of markers specific to molecules such as antibodies or highly affine ligands for the target.[1] The nature of the marker is critical, requiring an easy detection at sub-nanomolar concentrations. Therefore, developing versatile MS tags involves innovative chemistry, targeting precise functional groups.Specific probes such as ABP have been designed to selectively label biomolecules of interest, meeting the need for in vivo labeling. Conjugating MS-tags to peptides/proteins, modifying their ionization properties, enables discrimination between labeled and unlabeled biomolecules. This discrimination is ideal for detecting and quantifying low-abundance peptides in complex proteomes.[2]The objectives will focus here on modified model ABPs specifically functionalized to be evaluated in MALDI MS to undergo biological tests but also shape MALDI-MSI experiments.[3] These modified ABPs, specifically functionalized, hold promise for advancing biomolecule analysis and understanding complex biological processes.References1. Sejalon-Cipolla M, et al. Targeting out of range biomolecules: Chemical labelling strategies for qualitative and quantitative MALDI-MS based detection. TrAC - Trends Anal Chem. 2021;143.2. Paramelle D, et al. A new generation of cross-linkers for selective detection by MALDI MS. Proteomics. 2009;9(5):384-388.3. Kaminska M, et al. Ligand-Directed Modification of Active Matrix Metalloproteases: Activity-based Probes with no Photolabile Group. Angew Chemie Int Ed. 2021;60(18):18,272-18,279.