Chemistry and Molecular PharmacologyDesign, synthesis and structure of peptides and proteins

Design, 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.

Sánchez-Navarro M, Giralt E and Teixidó M.
Curr Opin Chem Biol, 38 134-140 (2017)
Lo Re D, Jones L, Giralt E and Murphy P.
Chem-Asian J, 11 (14), 2035-40 (2016)
Oller-Salvia B, Sánchez-Navarro M, Giralt E and Teixidó M.
Chem Soc Rev, 45 (17), 4690-707 (2016)
Oller-Salvia B, Sánchez-Navarro M, Ciudad S, Guiu M, Arranz-Gibert P, Garcia C, Gomis RR, Cecchelli R, García J, Giralt E and Teixidó M.
Angew Chem Int Edit, 55 (2), 572-5 (2016)
Arranz-Gibert P, Guixer B, Malakoutikhah M, Muttenthaler M, Guzmán F, Teixidó M and Giralt E.
J Am Chem Soc, 137 (23), 7357-64 (2015)
Arranz-Gibert P, Guixer B, Malakoutikhah M, Muttenthaler M, Guzman F, Teixidó M and Giralt E.
J Am Chem Soc, (2015)
Prades R, Oller-Salvia B, Schwarzmaier SM, Selva J, Moros M, Balbi M, Grazú V, de La Fuente JM, Egea G, Plesnila N, Teixidó M and Giralt E.
Angew Chem Int Edit, 54 (13), 3967-72 (2015)
Nevola L and Giralt E.
Chem Commun, 51 3302-3315 (2015)
Martín-Quirós A, Nevola L, Eckelt K, Madurga S, Gorostiza P and Giralt E.
Chem Biol, 22 (1), 31-7 (2015)
Moreno M, Zurita E, Giralt E.
J Control Release, 182 13-21 (2014)
Pujadas L, Rossi D, Andrés R, Teixeira CM, Serra-Vidal B, Parcerisas A, Maldonado R, Giralt E, Carulla N and Soriano E.
Nat Commun, 5 3443 (2014)
Serra-Vidal B, Pujadas L, Rossi D, Soriano E, Madurga S and Carulla N.
Acs Chem Biol, 9 (11), 2678-85 (2014)
Oller-Salvia B, Teixidó M and Giralt E.
Biopolymers, 100 (6), 675-86 (2013)
Nevola L, Martín-Quirós A, Eckelt K, Camarero N, Tosi S, Llobet A, Giralt E and Gorostiza P.
Angew Chem Int Edit, 52 (30), 7704-8 (2013)
Malakoutikhah M, Teixidó M and Giralt E.
Angew Chem Int Edit, 50 7998-8014 (2011)
Martín I, Teixidó M and Giralt E.
Chembiochem, 12 (6), 896-903 (2011)
Sánchez L, Madurga S, Pukala T, Vilaseca M, López-Iglesias C, Robinson CV, Giralt E and Carulla N.
J Am Chem Soc, 133 (17), 6505-8 (2011)
Carulla N, Zhou M, Giralt E, Robinson CV and Dobson CM.
Accounts Chem Res, 43 (8), 1072-9 (2010)
Gordo S, Martos V, Santos E, Menéndez M, Bo C, Giralt E and de Mendoza J.
P Natl Acad Sci Usa, 105 (43), 16426-31 (2008)
Pastor JJ, Granados G, Carulla N, Rabanal F and Giralt E
J Am Chem Soc, 129 14922-32 (2007)
Pujals S, Fernandez-Carneado J, Kogan M, Martinez J, Cavelier F and Giralt E
J Am Chem Soc, 128 8479-83 (2006)

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"

     

People

Group news & mentions

3 Oct 2017

The technology supplement Innovadores of the newspaper El Mundo has echoed on the award of 220,000 euros to three biomedical innovation projects underway at IRB Barcelona.

29 Sep 2017

The Catalan’ Government’s Agency for Management and of University and Research Grants (Agencia de Gestió i Ajuts Universitaris i de Recerca (AGAUR)) has awarded around 220,000 euros to thr

<p>Teresa Tarragó is co-founder of IProteos, an IRB Barcelona spinf-off (D. Portales)</p>
25 Sep 2017

Innovaspain.com has dedicated an article to the research undertaken by Iproteos, a company specialized in the discovery of drugs for diseases of the nervous system.

<p>Teresa Tarragó, CEO and co-founder of Iproteos</p>
23 Sep 2017

Agencia SINC echoes the interest of pharmaceutical multinationals in Iproteos. Founded in 2011 by Teresa Tarragó, this biotechnology company is a spin-off of IRB Barcelona.

Upcoming events

25 Oct
Aula Fèlix Serratosa, Parc Científic de Barcelona
Speaker:
Daniel Fisher. Centre national de la Recherche Scientifique(CNRS) Institute of Molecular Genetics (IGMM)
25 Oct
Aula Fèlix Serratosa, Parc Científic de Barcelona
Speaker:
Jody Rosenblatt, Ph.D. H. A. and Edna Benning Presidential Endowed Chair HHMI. Faculty Scholar Professor Huntsman Cancer Institute. Department of Oncological Sciences University of Utah
26 Oct
IRB Meeting Room 1 – IRB Administration Building, 1st Floor
Speaker:
Speaker: Alba Olivares, Technology Transfer Officer at IRB Barcelona