Chemistry and Molecular PharmacologyDesign, synthesis and structure of peptides and proteins
Our research focuses on three angles of peptide and protein chemistry : the design, synthesis and structure of bioactive molecules. From a structural perspective, we apply modern NMR techniques to study complex molecular recognition processes. Our group started in 1974 in the Organic Chemistry Department at the University of Barcelona. From the very beginning our activities centred on peptide molecules. However, over these years our focus has widened from synthesis to structure and biological activity and, at the same time, from peptides to larger biomolecules including small and medium-sized proteins.
Particular effort is devoted to the study of the dynamic properties of proteins and the design of specific ligands that interact with protein surfaces. Our group is also involved in applied science; this is reflected in the projects related to the therapeutic value of these molecules. In recent years, we have participated in studies on synthetic vaccines, inhibitors of amyloid protein aggregation, and anti-tumoural peptides from marine organisms.
a) Structure of Peptides and Proteins
Our goal is to perform conformational analysis and to complete the 3-D structural elucidation of peptides and proteins of biological interest. The molecules we address range from small cyclic depsipeptides of less than 10 residues to plant-protease inhibitors of more than 30,000 KDa. We use a variety of instrumental and computational tools; however, our research applies mainly high-field NMR.
b) Molecular Recognition
Our main focus is the design and synthesis of peptide molecules that recognize specific hot-spots on protein surfaces. We plan to use this knowledge to disrupt protein-protein interactions. From a methodological point of view, we use computational tools, mainly genetic algorithms, combinatorial chemistry, high-field NMR and fluorescence spectroscopy.
c) Peptides as Potential Therapeutic Agents
To date, the use of peptides as therapeutic agents involves more drawbacks than advantages. However, we consider that peptides still have practical applications in the design of drugs that are involved in protein-protein recognition events. Our activity in this field focuses on: the optimization of peptide ADME properties (especially blood-brain barrier permeability), the discovery of new drug delivery systems (proline-rich peptide dendrimers), and the development of inhibitors of amyloid formation (beta-amyloid peptide in Alzheimer’s disease and prion-related diseases).
d) Peptides in Nanobiotechnology
Our main focus is in the use of peptide-based nanoparticles for intracellular drug delivery. We follow two approaches: i) “only-peptide systems” based on the self assembly properties of amphipatic proline-rich peptides; and ii) “hybrid systems” made by conjugation of cell penetrating peptides with metal nanoparticles.
This group receives financial support from the following sources:
- Fundació "La Caixa" (RecerCaixa)
- Generalitat de Catalunya (Government of Catalonia)
- Friedrich’s Ataxia Research Alliance USA (FARA)
- Federación de Ataxias de España (FEDAES/GENEFA y BABELFAMILY)
- Fundació La Marató
- Ministerio de Economía y Competitividad (MINECO)
- European Commission (EC), Fondo Europeo de Desarrollo Regional (FEDER), "Una manera de hacer Europa"
Group news & mentions
Research into Alzheimer’s disease. Amyloid protein aggregates may perforate the neuronal cell membrane
New strategy to obtain a specific type of amyloid-beta aggregate that may underlie neuronal death in Alzheimer’s disease
Sights set on the next generation of shuttle peptides to target the brain
IRB Barcelona synthesizes molecules with anti-tumor potential
Group news & mentions
Extensive impact of Natàlia Carulla’s work at IRB Barcelona on a new method through which to study neuron death in Alzheimer’s disease.
The brains of millions of people suffering from Alzheimer´s disease are slowly and inescapably being depleted of neurons. However, the cause of neuronal death is still unknown.
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