RESEARCH
Functional Materials
Inspired by Nature’s repertoire of functional molecules, supramolecular chemistry evolved into a powerful strategy to assemble functional systems that can self-sort, self-heal, adapt, exchange, replicate or even transcribe. The exploitation of this dynamic features is particularly appealing to control multifactorial biological problems that require the interaction with multiple targets and stimuli-responsiveness to different chemical environments. However, these superstructures prepared based on noncovalent interactions involving ions and molecules in complexes often display poor stability, particularly in solution, and they are frequently difficult to characterize. Reversible covalent bonds, that depending on the conditions can be as labile as non-covalent interactions or as permanent as covalent bonds have the potential to enable the construction of more stable and well define molecular systems that may respond to specific disease associated stimuli.
In this emerging area of chemical biology we are exploring the reversible coordination chemistry of boron centers to assemble functional complexes with suitable properties to interfere with biological processes associated with cancer, neurodegeneration and protein misfolding.
Active areas of research include:
1. Discovery of new responsive molecules
2. Design of stimuli-responsive linkers for bioconjugates
3. Modular fluorophore platforms for bioimaging applications.
Protein Functionalization
The chemical functionalization of proteins is a strategy of paramount importance to study fundamental biological processes, though the marginal stability of proteins and the overabundance of functionalities make this an overwhelming challenge as these reactions need to be fast, selective, conducted with high yields in aqueous media at low concentrations, physiological pH, temperature and pressure.
Continuing a long standing interest in the design of new synthetic methodologies and on the use of water as a reaction media, we are now developing a series of methodologies to functionalize proteins with a particular focus on technologies that enable the reversible and/or orthogonal modification of the biomolecule.
Active areas of research include:
1. Development of reversible bioconjugation methods
2. Orthogonal and site-selective bioconjugation methods exploring Cys, Lys and N-terminal residues
3. Proximity driven bioconjugation methods
Targeted Therapy
In recent years, the use multifunctional constructs in which biomolecules like peptides and proteins, small vitamins or nucleic acids are endowed with the properties of specific payloads has emerged as leading therapeutics in oncology. Extensive studies in this area clearly suggest that the clinical success of bioconjugates is intimately related with the chemistries used to connect the functional components. Therefore, we are studying new formats of bioconjugates for drug delivery for oncology. The focus is to discover new bioconjugation methods and linker technologies that may be used to generate targeting drug conjugates with more well-defined structures and with mechanisms that trigger a therapeutic action as a direct response to the disease chemical environment.
