CHEMICAL BIOLOGY
Group Leader: Gemma Triola
Chemical Biology is a discipline that studies the biological processes using chemical tools. In the last two decades there has been remarkable achievements in Biology specially due to the application of chemical approaches based in the synthesis of molecules that are able to tune enzymatic activity or disrupt protein-protein interactions, design of new fluorescent probes, novel proteomic methods that allow the identification of new cellular targets and the development of techniques for the synthesis and modification of proteins.
Our main goal is the use of chemical tools to study and characterize diseases, and improve our knowledge of important biological phenomena, principally autophagy, lipid-protein interactions, signaling pathways such as Sonic Hedgehog and K-ras, and the regulation of the transcription by the design of artificial transcription factors. As a result, our scientific interests span organic chemistry, biochemistry, biophysics and medicinal chemistry.
The main research lines of the group are:
- Design and synthesis of molecules (small molecules, peptides, peptidomimetics…) to study and modulate biological processes.
- Development of chemical tools to regulate and characterize autophagy.
These probe range from small molecules to peptides and lipid derivatives.
We have also set up collaboration projects with the group of Dr. R.P. Herrera and the group of Dr. P. Sanz, both from the ISQCH (CSIC-University of Zaragoza) directed to investigate the biological activity of squaramides and N-heterocyclic carbenes (NHC) Gold and Silver complexes. - New strategies for the synthesis and modification of peptides and proteins.
- Characterization of protein-protein, protein-lipid and protein DNA/RNA interactions.
We have initiated a project aimed to characterize the role of lipids in modulating the function of proteins and lipidated proteins. A proteomic approach has been employed to identify novel ceramide-binding proteins, a sphingolipid with a crucial role in controlling essential cellular processes such as apoptosis. Moreover, a lipidomics strategy has been developed with the aim of characterizing the lipid diversity present in lipid-modified proteins.
Scientific staff
Gemma Triola
Tenured Scientist
gemma.triola@iqac.csic.es
Juan Bautista Blanco
Tenured Scientist
juanbautista.blanco@iqac.csic.es
Lab people
Carla Busquets
Predoctoral Researcher
carla.busquets@iqac.csic.es
Iván Sánchez
Predoctoral Researcher
ivan.sanchez@iqac.csic.es
- Kinetic and Mechanistic Studies of Native Chemical Ligation with Phenyl α-Selenoester Peptides
Iván Sánchez-Campillo & Juan B. Blanco-Canosa
JACS Au 2024, 4, 11, 4374–4382 - Targeting vascular disrupting agent-treated tumor microenvironment with tissue-penetrating nanotherapy
Valeria Sidorenko, Pablo Scodeller, Ain Uustare, Ivan Ogibalov, Andrus Tasa, Olga Tshubrik, Liis Salumäe, Kazuki N. Sugahara, Lorena Simón-Gracia & Tambet Teesalu
Sci Rep 14, 17513 (2024). https://doi.org/10.1038/s41598-024-64610-7
- Dinuclear silver and gold bisNHC complexes as drug candidates for cancer therapy
Mireia Quintana, Alba Rodriguez-Rius, Alba Vellé, Sonia Vives, Pablo J. Sanz Miguel, Gemma Triola
Bioorganic & Medicinal Chemistry, Volume 67, 1, August 2022
- Dinuclear silver and gold bisNHC complexes as drug candidates for cancer therapy
Quintana, M., Rodriguez-Rius, A., Vellé, A., Vives, S., Sanz Miguel, P.J., Triola, G.
Bioorganic and Medicinal Chemistry, 67, art. no. 116814, 2022
- On the Utility of Chemical Strategies to Improve Peptide Gut Stability
Kremsmayr, T., Aljnabi, A., Blanco-Canosa, J.B., Tran, H.N.T., Emidio, N.B., Muttenthaler, M.
Journal of Medicinal Chemistry, 2022
- Polymeric Composite Dressings Containing Calcium-Releasing Nanoparticles Accelerate Wound Healing in Diabetic Mice
Perez-Amodio, S., Rubio, N., Vila, O.F., Navarro-Requena, C., Castaño, O., Sanchez-Ferrero, A., Marti-Munoz, J., Alsina-Giber, M., Blanco, J., Engel, E.
Advances in Wound Care, 10 (6), pp. 301-316. 2021
- Palmitoylation as a Key Regulator of Ras Localization and Function
Busquets-Hernández, C., Triola, G.
Frontiers in Molecular Biosciences, 8, art. no. 659861, . 2021
- Native Chemical Ligation via N-Acylurea Thioester Surrogates Obtained by Fmoc Solid-Phase Peptide Synthesis
Palà-Pujadas, J., Blanco-Canosa, J.B
Methods in Molecular Biology, 2133, pp. 141-161. 2020
- A hydroxylamine probe for profiling S-acylated fatty acids on proteins
Schulte-Zweckel, J., Dwivedi, M., Brockmeyer, A., Janning, P., Winter, R., Triola, G.
Chemical Communications, 55 (75), pp. 11183-11186. 2019
- Identification of benzo[cd]indol-2(1H)-ones as novel Atg4B inhibitors via a structure-based virtual screening and a novel AlphaScreen assay
Quintana, M., Bilbao, A., Comas-Barceló, J., Bujons, J., Triola, G.
European Journal of Medicinal Chemistry, 178, pp. 648-666. 2019
- Activity-Based Imaging of Acid Ceramidase in Living Cells
Yadira F. Ordóñez, José Luís Abad, Mazen Aseer, Josefina Casas, Virginie Garcia, Mireia Casasampere, Edward H. Schuchman, Thierry Levade, Antonio Delgado, Gemma Triola and Gemma Fabrias
J. Am. Chem. Soc., 2019
- Peptide Ligations by Using Aryloxycarbonyl‐o‐methylaminoanilides: Chemical Synthesis of Palmitoylated Sonic Hedgehog
Judith Palà‐Pujadas, Prof. Dr. Fernando Albericio, Dr. Juan B. Blanco‐Canosa
Angew. Chem. 2018, 130, 1 – 7
- A biochemical and genetic discovery pipeline identifies PLCδ4b as a nonreceptor activator of heterotrimeric G-proteins
Maziarz, M., Broselid, S., DiGiacomo, V., Park, J.-C., Luebbers, A., Garcia-Navarrete, L., Blanco-Canosa, J.B., Baillie, G.S., Garcia-Marcos, M.
Journal of Biological Chemistry, 293 (44), pp. 16964-16983. 2018
- One-Pot Peptide Ligation-Oxidative Cyclization Protocol for the Preparation of Short-/Medium-Size Disulfide Cyclopeptides
Spengler, J., Blanco-Canosa, J.B., Forni, L., Albericio, F.
Org Lett, 20 (14), 4306-4309(2018).
- Molecular mechanism of Gαi activation by non-GPCR proteins with a Gα-Binding and Activating motif.
de Opakua AI, Parag-Sharma K, DiGiacomo V, Merino N, Leyme A, Marivin A, Villate M, Nguyen LT, de la Cruz-Morcillo MA, Blanco-Canosa JB, Ramachandran S, Baillie GS, Cerione RA, Blanco FJ, Garcia-Marcos M.
Nat Commun. 2017 May 18;8:15163.
- High Affinity Immobilization of Proteins Using the CrAsH/TC
Schulte-Zweckel, J.; Rosi, F.; Sreenu, D.; Schroder, H.; Niemeyer, C. M.; Triola, G.
Tag. Molecules, 21, 2016
- Semisynthetic lipidated LC3 protein mediates membrane fusion.
Yang A, Li Y, Pantoom S, Triola G, Wu YW.
Chembiochem. 14 1296-300, 2013
- Algar WR, Blanco-Canosa JB, Manthe RL, Susumu K, Stewart MH, Dawson PE, Medintz IL.
Synthesizing and modifying peptides for chemoselective ligation and assembly into quantum dot-peptide bioconjugates.
Methods Mol Biol. 2013;1025:47-73.
- Specific inhibition of GPCR-independent G protein signaling by a rationally engineered protein.
Leyme A, Marivin A, Maziarz M, DiGiacomo V, Papakonstantinou MP, Patel PP, Blanco-Canosa JB, Walawalkar IA, Rodriguez-Davila G, Dominguez I, Garcia-Marcos M.
Proc Natl Acad Sci U S A. 2017 Nov 28;114(48):E10319-E10328.
- Concurrent Modulation of Quantum Dot Photoluminescence Using a Combination of Charge Transfer and Förster Resonance Energy Transfer: Competitive Quenching and Multiplexed Biosensing Modality.
Algar WR, Khachatrian A, Melinger JS, Huston AL, Stewart MH, Susumu K, Blanco-Canosa JB, Oh E, Dawson PE, Medintz IL.
J Am Chem Soc. 2017 Jan 11;139(1):363-372.
- Squaramides with cytotoxic activity against human gastric carcinoma cells HGC-27: synthesis and mechanism of action.
Quintana, M. Alegre-Requena, J.V., Marqués-López, E., Herrera, R.P., Triola, G.
Med. Chem. Commun MedChemComm 7, 550-61, 2016
- Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition).
Klionsky DJ, Abdelmohsen K, Abe A, Abedin MJ, Abeliovich H, Acevedo Arozena A, Adachi H, Adams CM, Adams PD et al.
Autophagy. 12 1-222, 2016
- Specificity of Lipoprotein Chaperones for the Characteristic Lipidated Structural Motifs of their Cognate Lipoproteins.
Mejuch T, van Hattum H, Triola G, Jaiswal M, Waldmann H.
Chembiochem. 16 2460-5, 2016
- Chemical tools for modulating autophagy.
Triola, G.
Tetrahedron 3 387–406, 2015
- Chemical Protein Synthesis Using a Second-Generation N-Acylurea Linker for the Preparation of Peptide-Thioester Precursors.
Blanco-Canosa JB, Nardone B, Albericio F, Dawson PE.
J Am Chem Soc. 2015 Jun 10;137(22):7197-209.
- Site-specific, reversible and fluorescent immobilization of proteins on CrAsH-modified surfaces for microarray analytics.
Schulte-Zweckel J, Rosi F, Sreenu D, Schröder H, Niemeyer CM, Triola G.
Chem Commun (Camb). 50 12761-4., 2014
- Structure Guided Design and Kinetic Analysis of Highly Potent Benzimidazole Inhibitors Targeting the PDEδ Prenyl Binding Site.
Zimmermann G, Schultz-Fademrecht C, Küchler P, Murarka S, Ismail S, Triola G, Nussbaumer P, Wittinghofer A, Waldmann H.
J Med Chem. 57 5435-48, 2014
- Interaction of the human N-Ras protein with lipid raft model membranes of varying degrees of complexity.
Vogel A, Nikolaus J, Weise K, Triola G, Waldmann H, Winter R, Herrmann A, Huster D.
Biol Chem. 2014, 395,779-89.
- Rotational and translational dynamics of ras proteins upon binding to model membrane systems.
Werkmüller A, Triola G, Waldmann H, Winter R.
Chemphyschem. 14 3698-705, 2013
- Synthesis of lipidated peptides.
Rosi F, Triola G.
Methods Mol Biol. 1047 161-89, 2013
