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 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.

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"

     

People

Group news & mentions

<p>The graphic shows a new class of prolyl oligopeptidase (POP) inhibitor. The inhibitor is able to reach the brain and bind to the POP protein, In yellow/red, the reactive group of the inhibitor that bind to the catalytic site of the protein (S Guardiola)</p>
17 Mai 2018

Un article publicat per investigadors de l’Institut de Recerca Biomèdica (IRB Barcelona) a Cell Chemical Biology descriu una nova classe d’inhibidors per a la proteïna POP (prolil oligopep

<p>Natàlia Carulla's team studies the associations of beta-amyloid. In the microscopy image, beta-amyloid clusters are observed in in vitro samples. (Bernat Serra-Vidal, IRB Barcelona)</p>
20 Abr 2018

Europa Press, El Economista, Technology Networks, News Medical, entre altres mitjans de comunicació, han publicat un article sobre un estudi liderat a l’IRB Barcelona que aporta la primera evidènci

<p>Illustrative image of how scientists have deciphered the covalent nature of beta-amyloid dimers, an article published in Analytical Chemistry. Authors: Marina Gay, IRB Barcelona, and Lorena Markovich</p>
17 Abr 2018

A dia d’avui, els dos biomarcadors més ben establerts per diagnosticar precoçment l’Alzheimer són la concentració de la proteïna beta-amiloide i de proteïna tau fosforilada en líqu

<p>Ernest Giralt</p>
14 Feb 2018

El químic Ernest Giralt (Viladecans, 1948) és el director del laboratori d

Upcoming events

28 Jun
Fèlix Serratosa Room, Parc Científic de Barcelona
Speaker:
Jorge Cordero, Nerea Sánchez, Laura Tiessler and Sara Vives