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Research Programmes

Chemistry & Molecular Pharmacology

Design, synthesis and structure of peptides and proteins

Ernest Giralt

Ernest Giralt

Group Leader
Professor (Organic Chemistry Dept. - UB)
Office Tel : +34 93 40 37125
Lab Tel : +34 93 403 71 27
e-mail : ernest.giraltirbbarcelona.org

Background

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.

Research Interests

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.

Research Lines

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.

Funding

This group receives financial support from the following sources:

  • Fundación BBVA (BBVA Foundation)
  • Ministerio Educación y Ciencia (Spanish Ministry of Science and Education)
  • Fundació "la Caixa" ("la Caixa" Foundation)
  • Generalitat de Catalunya (Government of Catalonia)
  • Secretaría de Estado de Cooperación Internacional (AECI)(Spanish Agency for International Cooperation)
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  • Generalitat de catalunya
  • Generalitat de catalunya. Salut
  • Universidad de Barcelona
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Institute for Research in Biomedicine (IRB Barcelona)
Parc Científic de Barcelona
C/ Baldiri Reixac 10
08028 Barcelona - Spain
Tel: +34 93 402 02 50 | Fax: +34 93 403 71 14
infoarrobairbbarcelona.org