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

16 Sep 2016

Amplia repercusión del trabajo de Natàlia Carulla en el IRB Barcelona sobre una nueva metodología para acometer el estudio de la muerte de las neuronas en Alzheimer.

<p>Beta amyloid protein and AD are strongly linked but the role of this protein in this disease remains elusive. Hippocampus of transgenic mice overexpressing amyloid beta. In blue, neuronal nuclei. In green, beta amyloid plaques (E.Verdaguer/S.Brox)</p>
13 Sep 2016

El cerebro de millones de personas con Alzheimer se va vaciando de neuronas lentamente de forma ineludible. Sin embargo, qué provoca la muerte de las neuronas es aún una incógnita.

<p>Shuttle peptides are molecules that have the capacity to transport drugs across the blood-brain barrier and thus treat diseases affecting the central nervous system</p>
26 Ago 2016

Los científicos del IRB Barcelona, ​​Benjamí Oller, Macarena Sánchez, Ernest Giralt y Meritxell Teixidó, del Laboratorio de Péptidos y Proteínas del programa de Química y Farmacología Molecular, fi

Upcoming events

03 Oct - 05 Oct
Institut d'Estudis Catalans (IEC), Barcelona
05 Oct
Fèlix Serratosa, Parc Científic de Barcelona
Speaker:
Brad Stith, University of Colorado Denver
06 Oct
Aula Fèlix Serratosa, Parc Científic de Barcelona
Speaker:
Prof. Graham Ellis-Davies, Department of Neuroscience, Mount Sinai School of Medicine, NY (USA)