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.

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

<p>Scheme of therapeutic concept designed by IRB Barcelona. The protein frataxina binds to peptide shuttle (blue), allowing the protein to cross the blood brain barrier and reach the brain (IRB Barcelona)</p>
14 Mar 2017

The associations of patients and families Babel Family and the Asociación Granadina de l

<p>Mice neurons with the Frataxin gene transfered. In yellow, localization of the frataxin protein in neurons (Picture: Díaz-Nido lab)</p>
14 Mar 2017

Several media have echoed the research project on Friedreich’s Ataxia at IRB Barcelona, funded by the associations of patients and families called the Babel Family and the Asociación Granadina de l

10 Mar 2017

The Generalitat’s (Catalan Government) Universities and Research website has echoed on the research performed by scientists at IRB Barcelona and the UB, namely a shuttle produced from a peptide pre

<p>Iproteos is currently performing the regulatory preclinical phase of its drug candidate for CIAS treatment.</p>
19 Dec 2016

The biotech company and IRB Barcelona spin off Iproteos, in collaboration with the Neuropsychopharmacology Group at the Universidad del Pa

Upcoming events

28 Mar
IRB Meeting Room 1 – IRB Administration Building 1st Floor
Speaker:
Speaker: Albert Farré, Brand Manager at Novartis Oncology
29 Mar
Aula Fèlix Serratosa, Parc Científic de Barcelona
Speaker:
Iracema Caballero, IBMB-CSIC
29 Mar
Aula Fèlix Serratosa, Parc Científic de Barcelona
Speaker:
Javier López-Rios, PhD Development and Evolution, Department of Biomedicine, University of Basel, Switzerland