Research Lab

(Bio)molecular Structure and Interactions by NMR

(Bio)molecular Structure and Interactions by NMR
Research Interests

Our main research interests are related to the application and development of solution state nuclear magnetic resonance (NMR) spectroscopy for structural analysis and the study of intermolecular interactions in biological and chemical systems. In the context of the functional analysis of catalytic systems and the understanding of molecular recognition processes we explore: (i) protein-ligand interactions in drug discovery; (ii) solute-solvent interactions; (iii) protein structure and dynamics (iv) new techniques in NMR.

Research Highlights
Studying intermolecular interactions in complex media

Cells are inherently crowded, under molecular crowding (MC) conditions specific molecular recognition events and interactions may occur, that could remain undetectable under diluted solutions. We have recently used NMR to study the formation of large molecular size protein complexes driven by protein-glycan interactions under MC conditions demonstrating that glycosylation can be a player in quinary structure and in the organization of the cellular environment at the molecular level (CHEM. EUR. J., 2017; 23, 13213). Another of our main research interests is the study of molecular recognition processes in alternative complex media. By combining different NMR experiments we have been studying ion-pair interactions in ionic liquids in order to understand their supramolecular structure and better explore their biochemical applications (MAGN. RESON. CHEM., 2018, 56, 127).

fig1Protein-Glycan Quinary Interactions in Crowding Environment Unveiled by NMR Spectroscopy


Structural insights into mucin glycosylation and recognition

Glycans play a key role in distinct molecular mechanisms in health and disease. In this context, the projects (IF/00780/2015 and PTDC/BIA-MIB/31028/2017) investigate the mucin-derived cancer-related glycophenotype. By employing NMR in tandem with molecular modeling and biophysical techniques, the projects exploit the structural features of mucin glycosylation (NAT. COMMUN. 2017; 5, 1959; CHEM. EUR. J. 2018; 24, 8382) and the molecular recognition of mucin-derived tumour-associated carbohydrate antigens (TACAs) (J. AM. CHEM. SOC. 2015, 137, 12438) for a structure-guided rational design of glycan-based cancer therapies.

fig2Structural Insights on Glycans for Cancer Therapies


Representative Projects

  • Evaluation of ionic liquids for CO2 capture in exhaust gases”, PETROBRAS SA., Total and Unit funding: €110,000, Eurico Cabrita (PI).
  • “Advances into the Glycome: From a structural viewpoint to function in human health and disease”, IF/00780/2015, FCT-MCTES, Total and Unit funding: €50,000, Filipa Marcelo (PI).
  • “Advances in MUC1 Glycan Cancer Antigens: From structure to function in the fight against cancer”, FCT-MCTES, Total funding: €238,195, Unit funding: €176,266, Filipa Marcelo (PI).

Selected Publications

Hall, JL; Sohail, A; Cabrita, EJ; Macdonald, C; Stockner, T; Sitte, HH; Angulo, J; MacMillan, F. 2020. Saturation transfer difference NMR on the integral trimeric membrane transport protein GltPh determines cooperative substrate binding. Scientific Reports, 10, DOI: 10.1038/s41598-020-73443-z
de Matos, AM; Blazquez-Sanchez, MT; Bento-Oliveira, A; de Almeida, RFM; Nunes, R; Lopes, PEM; Machuqueiro, M; Cristovao, JS; Gomes, CM; Souza, CS; El Idrissi, IG; Colabufo, NA; Diniz, A; Marcelo, F; Oliveira, MC; Lopez, O; Fernandez-Bolanos, JG; Datwyler, P; Ernst, B; Ning, K; Garwood, C; Chen, BN; Rauter, AP. 2020. Glucosylpolyphenols as Inhibitors of A beta-Induced Fyn Kinase Activation and Tau Phosphorylation: Synthesis, Membrane Permeability, and Exploratory Target Assessment within the Scope of Type 2 Diabetes and Alzheimer's Disease. JOURNAL OF MEDICINAL CHEMISTRY, 63, DOI: 10.1021/acs.jmedchem.0c00841
Oroz, J; Felix, SS; Cabrita, EJ; Laurents, DV. 2020. Structural transitions in Orb2 prion-like domain relevant for functional aggregation in memory consolidation. JOURNAL OF BIOLOGICAL CHEMISTRY, 295, DOI: 10.1074/jbc.RA120.015211
Macias-Leon, J; Bermejo, IA; Asin, A; Garcia-Garcia, A; Companon, I; Jimenez-Moreno, E; Coelho, H; Mangini, V; Albuquerque, IS; Marcelo, F; Asensio, JL; Bernardes, GJL; Joshi, HJ; Fiammengo, R; Blixt, O; Hurtado-Guerrero, R; Corzana, F. 2020. Structural characterization of an unprecedented lectin-like antitumoral anti-MUC1 antibody. CHEMICAL COMMUNICATIONS, 56, DOI: 10.1039/d0cc06349e
dos Santos, LM; Bernard, FL; Polesso, BB; Pinto, IS; Frankenberg, CC; Corvo, MC; Almeida, PL; Cabrita, E; Einloft, S. 2020. Designing silica xerogels containing RTIL for CO2 capture and CO2/CH4 separation: Influence of ILs anion, cation and cation side alkyl chain length and ramification. JOURNAL OF ENVIRONMENTAL MANAGEMENT, 268, DOI: 10.1016/j.jenvman.2020.110340