Chemistry and Molecular Pharmacology Design, 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 centered 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 addressed our efforts towards fighting against cancer, schizophrenia, infectious diseases, and Friedreich’s ataxia.

a) Structure of Peptides and Proteins
The purpose of our research is the conformational analysis and 3-D structural elucidation of peptides and proteins of biological interest with an especial focus on their dynamic behavior at molecular level. Our range goes from small cyclic depsipeptides of less than 10 residues to proteolytic enzymes of more than 70,000 molecular weight. We use a variety of instrumental and computational tools with a special focus however, on the use of high-field nuclear magnetic resonance.

b) Molecular Recognition
Our main focus is the design and synthesis of peptide molecules that are able to recognize specific hot-spots at protein surfaces. We 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
Peptides are destined to play a major role as therapeutic agents. Our laboratory in Barcelona is contributing to speeding up this process. On the one hand, we devote efforts to studying the molecular details and dynamics of the events that occur during molecular recognition at protein surfaces. On the other hand, we are discovering and designing peptides able to cross biological barriers. Our aim is to use these peptides as shuttles for targeting therapeutic agents to organs, tissues, or cells, with a special emphasis on drug delivery to the brain.

d) Peptides in Nanobiotechnology
Our main focus is in the use of peptides to facilitate passage of nanoparticles trough biological barriers. We are especially interested in: i) intracellular delivery and ii) brain delivery.

Pujols J, Peña-Díaz S, Lázaro DF, Peccati F, Pinheiro F, González D, Carija A, Navarro S, Conde-Giménez M, García J, Guardiola S, Giralt E, Salvatella X, Sancho J, Sodupe M, Fleming Outeiro T, Dalfó E, Ventura.
P Natl Acad Sci Usa, 115 10481-1048 (2018)
Dıaz-Perlas C, Oller-Salvia B, Sanchez-Navarro M, Teixidó M, Giralt E.
Chem Sci, (2018)
Guardiola S, Varese M, Sánchez-Navarro M, Vincke C, Teixido M, Garcia J, Muyldermans S and Giralt E.
Angew Chem Int Edit, 15 13843-1384 (2018)
Guardiola S, Prades R, Mendieta L, Brouwer AJ, Streefkerk J, Nevola L, Tarragó T, Liskamp RMJ, Giralt E.
Cell Chemical Biology, 25 1031-1037 (2018)
Guardiola S, Prades R, Mendieta L, Brouwer AJ, Streefkerk J, Nevola L, Tarragó T, Liskamp RMJ and Giralt E.
Cell Chemical Biology, (2018)
Vila-Farrés X, Parra-Millán R, Sánchez-Encinales V, Varese M, Ayerbe-Algaba R, Bayó N, Guardiola S, Pachón-Ibáñez ME, Kotev M, García J, Teixidó M, Vila J, Pachón J, Giralt E and Smani Y.
Sci Rep, 7 (1), 14683 (2017)
Sánchez-Navarro M, Teixidó M and Giralt E.
Accounts Chem Res, 50 (8), 1847-1854 (2017)
Sánchez-Navarro M, Teixidó M and Giralt E.
Nat Chem, 9 (8), 727-728 (2017)
Sánchez-Navarro M, Giralt E and Teixidó M.
Curr Opin Chem Biol, 38 134-140 (2017)
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)
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"