RESUMEN
Various analytical technologies have been developed for the study of target-ligand interactions. The combination of these technologies gives pivotal information on the binding mechanism, kinetics, affinity, residence time, and changes in molecular structures. Mass spectrometry (MS) offers structural information, enabling the identification and quantification of target-ligand interactions. Surface plasmon resonance (SPR) provides kinetic information on target-ligand interaction in real time. The coupling of MS and SPR complements each other in the studies of target-ligand interactions. Over the last two decades, the capabilities and added values of SPR-MS have been reported. This review summarizes and highlights the benefits, applications, and potential for further research of the SPR-MS approach.
Asunto(s)
Descubrimiento de Drogas , Espectrometría de Masas , Resonancia por Plasmón de Superficie , Resonancia por Plasmón de Superficie/métodos , Descubrimiento de Drogas/métodos , Espectrometría de Masas/métodos , Humanos , Ligandos , AnimalesRESUMEN
Dearomatization of indoles through a charge transfer complex constitutes a powerful tool for synthesizing three-dimensional constrained structures. However, the implementation of this strategy for the dearomatization of tryptamine-derived isocyanides to generate spirocyclic scaffolds remains underdeveloped. In this work, we have demonstrated the ability of tryptamine-derived isocyanides to form aggregates at higher concentration, enabling a single electron transfer step to generate carbon-based-radical intermediates. Optical, HRMS and computational studies have elucidated key aspects associated with the photophysical properties of tryptamine-derived isocyanides. The developed protocol is operationally simple, robust and demonstrates a novel approach to generate conformationally constrained spirocyclic scaffolds, compounds with high demand in various fields, including drug discovery.
RESUMEN
The native extracellular matrix (ECM) undergoes constant remodeling, where adhesive ligand presentation changes over time and in space to control stem cell function. As such, it is of interest to develop 2D biointerfaces able to study these complex ligand stem-cell interactions. In this study, a novel dynamic bio interface based on DNA hybridization is developed, which can be employed to control ligand display kinetics and used to study dynamic cell-ligand interaction. In this approach, mesoporous silica nanoparticles (MSN) are functionalized with single-strand DNA (MSN-ssDNA) and spin-coated on a glass substrate to create the 2D bio interface. Cell adhesive tripeptide RGD is conjugated to complementary DNA strands (csDNA) of 9, 11, or 20 nucleotides in length, to form csDNA-RGD. The resulting 3 csDNA-RGD conjugates can hybridize with the ssDNA on the MSN surface, presenting RGD with increased ligand dissociation rates as DNA length is shortened. Slow RGD dissociation rates led to enhanced stem cell adhesion and spreading, resulting in elongated cell morphology. Cells on surfaces with slow RGD dissociation rates also exhibited higher motility, migrating in multiple directions compared to cells on surfaces with fast RGD dissociation rates. This study contributes to the existing body of knowledge on dynamic ligand-stem cell interactions.
RESUMEN
Quorum sensing (QS) is a complex communication system in bacteria, directing their response to the environment. QS is also one of the main regulators of bacterial biofilms' formation, maturation and dispersion. Matrix-assisted laser desorption ionization (MALDI) mass spectrometry imaging (MSI) is a molecular imaging technique that allows the mapping of QS molecules in bacterial biofilms. Here, we highlight the latest advances in MALDI-MSI in recent years and how this technology can improve QS understanding at the molecular level.