We are a medicinal chemistry laboratory with a keen interest in carbohydrates and their applications in biology and medicine. We strive for developing creative and efficient synthetic strategies for synthesizing biologically active saccharides associated with neglected tropical diseases and re-emerging pathogens.
Synthetic methods in carbohydrate chemistry: Carbohydrates are, probably, the most understudied class of biomolecules. From a synthetic chemist's perspective, their structural complexity is a source of inspiration for developing creative synthetic methods to enable access to their appealing molecular architectures. Highly stereoselective glycosylation reactions and the minimal use of protecting groups are special challenges we consider when planning our work. We are currently working on developing non-conventional synthetic methods in carbohydrate chemistry including electrosynthesis, organometallic, and free radical methods for preparing carbohydrate antigens, rare bacterial monosaccharides, and glycomimetic drug candidates.
Carbohydrate antigens associated with neglected diseases: According to the CDC, more than 1 billion people in the world suffer from neglected tropical diseases (NTDs) and neglected parasitic infections (NPIs). The economically disfavored populations living in the Asian, African, and Latin American continents are the most affected by NPDs and NPIs. However, these ailments are not exclusive to developing countries. Over 300,000 people living in the US are infected with Trypanosoma cruzi -the etiological agent of Chagas disease- and Leishmaniasis (another protozoal infection) is endemic in all of the southern Europe countries. Current projects in this area are focused on synthesizing carbohydrate antigens of Trypanosoma cruzi, Schistosoma mansoni, and Leishmania donovani for further development of immunotherapies and diagnostic tools.
Synthesis of high-affinity ligands for neutralizing bacterial toxins: Bordetella pertussis (whooping cough), Vibrio cholerae (cholera) and Clostridium difficile (nosocomial diarrhea) are examples of pathogenic bacteria that release protein toxins as a major virulence factor. The structure of these toxins include a catalytic domain, responsible for the toxic effects, and a carbohydrate recognition domain (CRD) in charge of binding the sugar receptors at the cell surface of the target tissues for subsequent toxin uptake. Current projects aimed to address this problem involve the design and synthesis of carbohydrate-based small-molecule inhibitors of the CRD of Bordetella pertussis toxin Ptx and the investigation of bifunctional molecules to design better toxin ligands.