Group Leader/s
Head of lab
intro
The research interests of the CCG group lie at the interface between Chemistry and Biology, by means of molecular modeling and computational chemistry applied to the understanding of ligand-receptor interactions and molecular recognition processes relevant for drug design. We combine these investigations with structural studies, synthesis of compounds and biological studies in close collaboration with international groups, within a multidisciplinary and integrative approach.
We are focused on the study of the molecular recognition processes involving Pattern Recognition Receptors (PRRs), such as Toll-like receptors (main actors in innate immunity), and Galectins (beta-galactoside-binding lectins that play an important role in infection, inflammatory diseases and tumor progression). Despite the number of available 3D structures, the molecular basis of the interaction and response, at atomic level, are still elusive. The global goal is to understand the molecular details of ligand recognition as a source of new compounds able to modulate the target behaviour with possible therapeutic applications.
Members
| Sonsoles Martin Santamaria |
| Joan Guzman Caldentey |
| Elena Gómez Rubio |
| Diego Sanz Martín |
| Miren Itziar Alcorta Calvo |
Selected Publications
Sestito SE, Facchini FA, Morbioli I, Billod JM, Martin-Santamaria S, Casnati A, Sansone F, Peri F. [2017]. Amphiphilic Guanidinocalixarenes Inhibit Lipopolysaccharide (LPS)- and Lectin-Stimulated Toll-like Receptor 4 (TLR4) Signaling. J. Med. Chem. 2017, 60, 4882–4892. Issue cover.
El-Halfawy OM, Klett J, Ingram RJ, Loutet SA, Murphy ME, Martín-Santamaría S, Valvano MA. [2017]. Antibiotic Capture by Bacterial Lipocalins Uncovers an Extracellular Mechanism of Intrinsic Antibiotic Resistance. mBio, 8(2). pii: e00225-17.
Pérez-Regidor L, Zarioh M, Ortega L, Martín-Santamaría S.* [2016]. Virtual Screening Approaches towards the Discovery of Toll-Like Receptor Modulators. Int. J. Mol. Sci. 2016, 17(9). pii: E1508.
Vašl J, Oblak A, Peternelj TT, Klett J, Martín-Santamaría S, Gioannini TL, Weiss JP, Jerala R. [2016]. Molecular Basis of the Functional Differences between Soluble Human Versus Murine MD-2: Role of Val135 in Transfer of Lipopolysaccharide from CD14 to MD-2. J. Immunol. 2016, 196, 2309-18.
Billod JM, Lacetera A, Guzmán-Caldentey J, Martín-Santamaría S.* [2016]. Computational Approaches to Toll-Like Receptor 4 Modulation. Molecules, 2016, 21(8). pii: E994.
Ciaramelli C, Calabrese V, Sestito SE, Pérez-Regidor L, Klett J, Oblak A, Jerala R, Piazza M, Martín-Santamaría S,* Peri F.* [2016]. Glycolipid-based TLR4 modulators and fluorescent probes: rational design, synthesis and biological properties. Chem. Biol. & Drug Des. 2016, 88, 217-29.
Ghirardello M, de Las Rivas M, Lacetera A, Delso I, Lira-Navarrete E, Tejero T, Martín-Santamaría S,* Hurtado-Guerrero R,* Merino P.* [2016]. Glycomimetics Targeting Glycosyltransferases: Synthetic, Computational and Structural Studies of Less-Polar Conjugates. Chem. A. Eur. J. 22, 7215-24.
Di Lorenzo F, Kubik Ł, Oblak A, Lorè NI, Cigana C, Lanzetta R, Parrilli M, Hamad MA, De Soyza A, Silipo A, Jerala R, Bragonzi A, Valvano MA, Martín-Santamaría S,* Molinaro A.* [2015]. Activation of human TLR4/MD-2 by hypoacylated lipopolysaccharide from a clinical isolate of Burkholderia cenocepacia. J. Biol. Chem. 2015, 290, 21305-19.
Molinaro A,* Holst O, Di Lorenzo F, Callaghan M, Nurisso A, D´Errico G, Zamyatina A, Peri F, Berisio R, Jerala R, Jiménez-Barbero J, Silipo A, Martín-Santamaría S.* [2015]. Chemistry of lipid A: at the heart of innate immunity. Chem. A Eur. J. 21, 500-19.
Xu B, Unione L, Sardinha J, Wu S, Ethève-Quelquejeu M, Pilar Rauter A, Blériot Y, Zhang Y, Martín-Santamaría S, Díaz D, Jiménez-Barbero J, Sollogoub M [2014]. gem-Difluorocarbadisaccharides: Restoring the exo-Anomeric Effect. Angew. Chem. Int. Ed. Engl. 2014, 53, 9597-602.
Vidal P, Roldós V, Fernández-Alonso Mdel C, Vauzeilles B, Bleriot Y, Cañada FJ, André S, Gabius HJ, Jiménez-Barbero J,* Espinosa JF,* Martín-Santamaría S.* [2013]. Conformational selection in glycomimetics: human galectin-1 only recognizes syn-Ψ-type conformations of β-1,3-linked lactose and its C-glycosyl derivative. Chem. Eur. J. 19, 14581-90.
Funding
Current funding
MINECO. CTQ2014-57141-R. Molecular Pattern Recognition Receptors: Computational Chemistry Insights for Drug Design and Innate Immunity Modulation.
Marie Skłodowska-Curie Actions. Innovative Training Networks. H2020-MSCA-ITN-2014. “TOLLerant” Toll-Like Receptor 4 activation and function in diseases: an integrated chemical-biology approach. www.tollerant.eu
Past funding
MINECO. CTQ2011-22724. Molecular recognition processes of therapeutic targets involved in immunity and bacterial infection. Approaches from the Computational Chemistry.
Marie Curie Initial Training Networks FP7-PEOPLE-2012-ITN 317297. “GLYCOPHARM. The Sugar Code: from (bio)chemical concept to clinics”. www.glycopharm.eu
COST Action BM1003. “Microbial cell Surface determinants of virulence as targets for new therapeutics in cystic fibrosis”. www.cost-bm1003.info/