@article {7574, title = {The Quest for Anticancer Vaccines: Deciphering the Fine-Epitope Specificity of Cancer-Related Monoclonal Antibodies by Combining Microarray Screening and Saturation Transfer Difference NMR}, journal = {J. Am. Chem. Soc.}, volume = {137}, year = {2015}, pages = {12438-12441}, author = {Helena Coelho and Matsushita, T. and G Artigas and H Hinou and FJ Ca{\~n}ada and R Lo-Man and C Leclerc and Cabrita, E. J. and J Jim{\'e}nez-Barbero and S-I Nishimura and F Garcia-Mart{\'\i}n and F Marcelo} } @article {7572, title = {A rational approach to sustainable CO2-capture by imidazolium ionic liquids: tuning CO2 solubility by cation alkyl branching}, journal = {Chem. Sus. Chem.}, volume = {8}, year = {2015}, pages = {1935-1946}, author = {Corvo, Marta C. and Sardinha, Jo{\~a}o and Casimiro, Teresa and Marin, Graciane and Seferin, Marcus and Einloft, Sandra and Menezes, Sonia C. and Dupont, Jairton and Cabrita, Eurico J.} } @article {7573, title = {Rationalizing the role of the anion in CO2 capture and conversion using imidazolium-based ionic liquid modified mesoporous s{\'\i}lica}, journal = {RSC Advances}, volume = {5}, year = {2015}, pages = {64220-64227}, author = {Aquino, Aline S and Bernard, FL and Borges, JV and Mafra, Luis and Dalla Vecchia, Felipe and Vieira, MO and Ligabue, R and Chaban, VV and Cabrita, E. J. and Einloft, S} } @article {7410, title = {Synthesis and evaluation of new benzimidazole-based COX inhibitors: a naproxen-like interaction detected by STD-NMR}, journal = {RSC Advances}, volume = {5}, year = {2015}, pages = {49098-49109}, abstract = {

Non-steroidal anti-inflammatory drugs exert their pharmacological activity through inhibition of cyclooxygenase 1 and 2 (COX-1 and COX-2). Recent research suggests that a balanced inhibition of both COX-1 and COX-2 is the key to reduce the side-effects exhibited by COX inhibitors. We developed new benzimidazole-based compounds that showed a balanced COX inhibition, supported by molecular docking screening. The human whole blood assays demonstrated that the ester derivatives were potent inhibitors. Competitive saturation transfer difference (STD)-NMR experiments, in the presence of COX-2, using naproxen and diclofenac demonstrated that ester derivatives do not compete with diclofenac for the same binding site, but compete with the allosteric inhibitor naproxen. Combination of NMR spectroscopy with molecular docking has permitted us to detect a new naproxen-like inhibitor, which could be used for future drug development.

}, url = {http://pubs.rsc.org/en/content/articlelanding/2015/ra/c5ra04984a$\#$!divAbstract}, author = {L. C. R. Carvalho and Ribeiro, D and R. S. G. R. Seixas and A. M .S. Silva and M. Nave and A. C. Martins and S. Erhardt and Fernandes, E and Cabrita, E. J. and M. M. B. Marques} } @article {5838, title = {Assessing diffusion in enzyme loaded sol{\textendash}gel matrices}, journal = {RSC Advances}, volume = {4}, year = {2014}, pages = {25099-25105}, abstract = {

Pulsed field gradient spin echo high resolution magic angle spinning nuclear magnetic resonance spectroscopy is a powerful technique to characterize confined biosystems. We used this approach to assess the diffusion of solvent and reaction species within sol{\textendash}gel matrices differing in enzyme loading.

}, url = {http://pubs.rsc.org/en/content/articlelanding/2014/ra/c4ra01620c$\#$!divAbstract}, author = {Barreira, Gustavo and Ferreira, Ana S. D. and Pedro Vidinha and Cabral, Joaquim M. S. and Martinho, Jos{\'e} M. G. and Lima, Jo{\~a}o Carlos and Cabrita, Eurico J. and Barreiros, Susana} } @article {6485, title = {Delineating binding modes of Gal/GalNAc and structural elements of the molecular recognition of tumor-associated mucin glycopeptides by the human macrophage galactose-type lectin}, journal = {Chem. Eur. J.}, volume = {in press}, year = {2014}, abstract = {

The human macrophage galactose-type lectin (hMGL) is a key physiological receptor for the carcinoma-associated Tn antigen (GalNAc-α-1-O-Ser/Thr) in mucins. We herein report NMR- and modeling-based data on the molecular recognition features of synthetic Tn-bearing glycopeptides by hMGL. Cognate epitopes on the sugar and matching key amino acids involved in the interaction have been identified by saturation transfer difference (STD) NMR spectroscopy. Only the amino acids close to the glycosylation site in the peptides are involved in lectin contact. Moreover, control experiments with non-glycosylated MUC1 peptides unequivocally showed that the sugar residue is essential for hMGL binding, as is Ca2+. The dissociation constants (Kd) have been estimated by STD titrations and/or STD competition experiments and show that Gal was a poor binder for hMGL, with a Kd in the mM range, while GalNAc and MUC1 Tn-glycopetides reached Kd values in the lower μM range. STD-based results suggested a distinct interacting epitope for the two monosaccharides. NMR data have been complemented with molecular dynamics simulations and Corcema- ST to establish a 3D view on the molecular recognition process between Gal, GalNAc and the Tn-presenting glycopeptides and hMGL. Gal and GalNAc have a dual binding mode with opposite trend of the main interaction pattern and the differences in affinity can be explained by additional hydrogen bonds and CH-π contacts involving exclusively the NHAc moiety.

}, author = {Marcelo, Filipa and Fayna Garcia-Martin and Takahiko Matsushita and Sardinha, Jo{\~a}o and Helena Coelho and Anneloes Oude-Vrielink and Christiane Koller and Sabine Andr{\'e} and Cabrita, Eurico J. and Hans-Joachim Gabius and Shin-Ichiro Nishimura and Jes{\'u}s Jim{\'e}nez-Barbero and F. Javier Ca{\~n}ada} } @article {5698, title = {Inhibition of LOX by flavonoids: a structure-activity relationship study.}, journal = {European Journal of Medicinal Chemistry}, volume = {72}, year = {2014}, pages = {137-145}, abstract = {

The lipoxygenase (LOX) products have been identified as mediators of a series of inflammatory diseases, namely rheumatoid arthritis, inflammatory bowel disease, psoriasis, allergic rhinitis, atherosclerosis and certain types of cancer. Hence, LOX inhibitors are of interest for the modulation of these phenomena and resolution of the inflammatory processes. During LOX activity, peroxyl radical complexes are part of the reaction and may function as sources of free radicals. Thus antioxidants, such as flavonoids, capable of inhibiting lipid peroxidation and scavenging free radicals, may act as LOX inhibitors. The aim of this work was to assess the structure{\textendash}activity relationship among a series of flavonoids concerning 5-LOX inhibition, through a systematic study of the inhibition of the formation of LTB4 in human neutrophils. The type of inhibition of the flavonoids was further studied using soybean LOX, type I, and Saturation Transfer Difference 1H NMR (STD-1H NMR) was used to characterize the binding epitopes of the compounds to LOX-1. The obtained results reinforce flavonoids as effective inhibitors of LTB4 production in human neutrophils. It was also possible to establish a structure/activity relationship for the inhibitory activity and the type of inhibition.

}, url = {http://www.sciencedirect.com/science/article/pii/S0223523413007721}, author = {Ribeiro, D and Freitas, M and Tom{\'e}, SM and Silva, AM and Porto, G and Cabrita, E. J. and Marques, M. M. and Fernandes, E} } @article {3739, title = {Molecular Recognition of Rosmarinic Acid from Salvia sclareoides Extracts by Acetylcholinesterase: A New Binding Site Detected by NMR Spectroscopy}, journal = {Chemistry: A European Journal}, volume = {19}, year = {2013}, pages = {6641-6649}, abstract = {

Acetylcholinesterase (AChE) inhibition is one of the most currently available therapies for the management of Alzheimer{\textquoteright}s disease (AD) symptoms. In this context, NMR spectroscopy binding studies were accomplished to explain the inhibition of AChE activity by Salvia sclareoides extracts. HPLC-MS analyses of the acetone, butanol and water extracts eluted with methanol and acidified water showed that rosmarinic acid is present in all the studied samples and is a major constituent of butanol and water extracts. Moreover, luteolin 4'-O-glucoside, luteolin 3',7-di-O-glucoside and luteolin 7-O-(6''-O-acetylglucoside) were identified by MS2 and MS3 data acquired during the LC-MSn runs. Quantification of rosmarinic acid by HPLC with diode-array detection (DAD) showed that the butanol extract is the richest one in this component (134 μg mg-1 extract). Saturation transfer difference (STD) NMR spectroscopy binding experiments of S. sclareoides crude extracts in the presence of AChE in buffer solution determined rosmarinic acid as the only explicit binder for AChE. Furthermore, the binding epitope and the AChE-bound conformation of rosmarinic acid were further elucidated by STD and transferred NOE effect (trNOESY) experiments. As a control, NMR spectroscopy binding experiments were also carried out with pure rosmarinic acid, thus confirming the specific interaction and inhibition of this compound against AChE. The binding site of AChE for rosmarinic acid was also investigated by STD-based competition binding experiments using Donepezil, a drug currently used to treat AD, as a reference. These competition experiments demonstrated that rosmarinic acid does not compete with Donepezil for the same binding site. A 3D model of the molecular complex has been proposed. Therefore, the combination of the NMR spectroscopy based data with molecular modelling has permitted us to detect a new binding site in AChE, which could be used for future drug development.

}, url = {http://doi.org/10.1002/chem.201203966}, author = {Marcelo, Filipa and Dias, Catarina and Madeira, Paulo J. and Jorge, Tiago and Flor{\^e}ncio, M. Helena and Canada, F. Javier and Cabrita, Eurico J. and Jim{\'e}nez-Barbero, J{\'e}sus and Rauter, Amelia P.} } @article {4595, title = {NMR Solution Structure and SRP54M predicted interaction of the N-Terminal sequence (1-30) of the ovine Doppel protein}, journal = {Peptides}, volume = {49}, year = {2013}, pages = {32-40}, abstract = {

Prion protein (PrPC) biosynthesis involves a multi-step process that includes translation and post-translational modifications. While PrP has been widely investigated, for the homolog Doppel (Dpl), limited knowledge is available. In this study, we focused on a vital step of eukaryotic protein biosynthesis: targeting by the signal recognition particle (SRP). Taking the ovine Dpl (OvDpl(1-30)) peptide as a template, we studied its behavior in two different hydrophobic environments using CD and NMR spectroscopy. In both trifluoroethanol (TFE) and dihexanoyl-sn-glycero-3-phosphatidylcholine (DHPC), the OvDpl(1-30) peptide revealed to fold in an alpha-helical conformation with a well-defined central region extending from residue Cys8 until Ser22. The NMR structure was subsequently included in a computational docking complex with the conserved M-domain of SRP54 protein (SRP54M), and further compared with the N-terminal structures of mouse Dpl and bovine PrPC proteins. This allowed the determination of (i) common predicted N-terminal/SRP54M polar contacts (Asp331, Gln335, Glu365 and Lys432) and (ii) different N{\textendash}C orientations between prion and Dpl peptides at the SRP54M hydrophobic groove, that are in agreement with each peptide electrostatic potential. Together, these findings provide new insights into the biosynthesis of prion-like proteins. Besides they also show the role of protein conformational switches in signalization toward the endoplasmic membrane, a key event of major significance in the cell cycle. They are thus of general applicability to the study of the biological function of prion-like as well as other proteins.

}, url = {http://dx.doi.org/10.1016/j.peptides.2013.08.013}, author = {Jorge Pimenta and Viegas, Aldino and Sardinha, Jo{\~a}o and Martins, Ivo C and Cabrita, Eurico J. and Fontes, Carlos M. G. A. and Prates, Jose A. M. and Pereira, Rosa M. L. N.} } @article {4998, title = {Protein destabilisation in ionic liquids: the role of preferential interactions in denaturation}, journal = {Phys. Chem. Chem. Phys.}, year = {2013}, pages = {19632-19643}, abstract = {

The preferential binding of anions and cations in aqueous solutions of the ionic liquids (ILs) 1-butyl- 3-methylimidazolium ([C4mim]+) and 1-ethyl-3-methylimidazolium ([C2mim]+) chloride and dicyanamide (dca-) with the small alpha-helical protein Im7 was investigated using a combination of differential scanning calorimetry, NMR spectroscopy and molecular dynamics (MD) simulations. Our results show that direct ion interactions are crucial to understand the effects of ILs on the stability of proteins and that an anion effect is dominant. We show that the binding of weakly hydrated anions to positively charged or polar residues leads to the partial dehydration of the backbone groups, and is critical to control stability, explaining why dca- is more denaturing than Cl-. Direct cation{\textendash}protein interactions also mediate stability; cation size and hydrophobicity are relevant to account for destabilisation as shown by the effect of [C4mim]+ compared to [C2mim]+. The specificity in the interaction of IL ions with protein residues established by weak favourable interactions is confirmed by NMR chemical shift perturbation, amide hydrogen exchange data and MD simulations. Differences in specificity are due to the balance of interaction established between ion pairs and ion-solvent that determine the type of residues affected. When the interaction of both cation and anion with the protein is strong the net result is similar to a non-specific interaction, leading ultimately to unfolding. Since the nature of the ions is a determinant of the level of interaction with the protein towards denaturation or stabilisation, ILs offer a unique possibility to modulate protein stabilisation or even folding events.

}, url = {http://pubs.rsc.org/en/Content/ArticleLanding/2013/CP/c3cp53395f$\#$!divAbstract}, author = {Angelo Miguel Figueiredo and Sardinha, Jo{\~a}o and Moore, Geoffrey R. and Cabrita, Eurico J.} } @article {3233, title = {Solution Structure, Dynamics and Binding Studies of a Family 11 Carbohydrate-Binding Module from Clostridium thermocellum (CtCBM11)}, journal = {Biochemical Journal}, volume = {451}, year = {2013}, pages = {289-300}, abstract = {

Non-catalytic cellulosomal carbohydrate-binding modules (CBMs) are responsible for increasing the catalytic efficiency of cellulosic enzymes by selectively putting the substrate (a wide range of poly- and oligosaccharides) and enzyme into close contact. In the present work we carried out an atomistic rationalization of the molecular determinants of ligand specificity of a family 11 CBM from thermophilic C. thermocellum (CtCBM11), based on a NMR and molecular modeling approach. We have determined the NMR solution structure of CtCBM11 at 25 and 50 {\textordmasculine}C and derived information on the residues of the protein involved in ligand recognition and on the influence of the length of the saccharide chain on binding. We obtained models of the CtCBM11/cellohexaose and CtCBM11/cellotetraose complexes by docking in accordance with the NMR experimental data. Specific ligand/protein CH-π and Van der Waals interactions were found to be determinant for the stability of the complexes and for defining specificity. Using the order parameters derived from backbone dynamics analysis in the presence and absence of ligand and at 25 and 50 {\textordmasculine}C, we determined that the protein{\textquoteright}s backbone conformational entropy is slightly positive. This data in combination with the negative binding entropy calculated from ITC studies supports a selection mechanism where a rigid protein selects a defined oligosaccharide conformation.

}, url = {http://dx.doi.org/10.1042/BJ20120627}, author = {Viegas, Aldino and Sardinha, Jo{\~a}o and Duarte, Daniel F and Carvalho, Ana Luisa and Fontes, Carlos M. G. A. and Romao, Maria Joao and Macedo, Anjos L and Cabrita, Eurico J.} } @article {4783, title = {Solvation of CO2 in [C4mim][BF4] and [C4mim][PF6] ionic liquids revealed by High Pressure NMR}, journal = {Angewandte Chemie International Edition}, volume = {49}, year = {2013}, pages = {13024-13027}, url = {http://dx.doi.org/:10.1002/anie.201305630}, author = {Corvo, Marta C. and Sardinha, Jo{\~a}o and Menezes, Sonia C. and Einloft, Sandra and Seferin, Marcus and Dupont, Jairton and Casimiro, Teresa and Cabrita, Eurico J.} } @article {3114, title = { Antifungals on paper conservation: An overview }, journal = {International Biodeterioration \& Biodegradation}, volume = {74}, year = {2012}, pages = {67-84}, abstract = {

Since its invention, paper has become one of the main carriers of our cultural, scientific, political, economic and historical information. Given the importance of this material, its preservation is a matter of great interest. Paper can be deteriorated due to physical, chemical and biological agents. Within microorganisms, fungi are the major paper biodeteriogens. Throughout history, several methods have been used to prevent and stop fungal deterioration on paper based materials. In this work we present a review of the main chemical and physical methods used to avoid fungal paper biodeterioration until nowadays and also of some new approaches tested recently. The advantages and disadvantages of these methods are discussed as well as their health effects. Studies regarding antifungal compositions, methods of application, performance and effects on the treated materials are also presented with the aim of providing a clear set of conclusions on the topic. (C) 2012 Elsevier Ltd. All rights reserved.

}, author = {S{\'\i}lvia Sequeira and Cabrita, Eurico J. and Filomena M. Macedo} } @article {3113, title = { Thymus mastichina: Chemical Constituents and their Anti-cancer Activity }, journal = {Natural Product Communications}, volume = {7}, year = {2012}, pages = {1491-1494}, author = {Joana Gordo and Patr{\'\i}cia M{\'a}ximo and Eurico Cabrita and Ana Louren{\c c}o and Abel Oliva and Joana Almeida and Mariana Filipe and Pedro Cruz and Rita Barcia and Miguel Santos and Helder Cruz} } @article {2272, title = {Indole based cyclooxygenase inhibitors: synthesis, biological evaluation, docking and NMR screening}, journal = {European Journal of Medicinal Chemistry}, volume = {54}, year = {2012}, pages = {823-833}, abstract = {

The close structural similarity between the two cyclooxygenase (COXs) isoforms and the absence of selective inhibitors without side effects continues to stimulate the development of novel approaches towards selective anti-inflammatory drugs. In the present study a small library of new indolic compounds involving two different substitutions patterns at the indole scaffold was synthesized. In order to establish a relation between the spatial distribution of known functional groups related with inhibitory activity, two substitution patterns were explored: one with substituents at N-1, C-3, C-5 positions and another at C-2, C-3 and C5 positions. Accordingly, indole positions C-5, C-3 and N-1 were substituted with: sulfonamide or methylsulfone at C-5, p-halo-benzyl group at C-3, and an alkyl chain with a trifluoromethyl group at N-1. Alternatively, a p-halo-benzyl group was introduced at C-2, leaving the indolic nitrogen free. Inhibitory studies were performed and the activity results obtained against both COXs isoforms were rationalized based on docking and NMR studies. Docking studies show that dialkyation at C-2 and C-3 favors a binding with an orientation similar to that of the known selective inhibitor SC-558. From the tested compounds, this substitution pattern is correlated with the highest inhibitory activity and selectivity: 70\% COX-2 inhibition at 50 M, and low COX-1 inhibition (18{\textpm}9\%). Additionally, Saturation Transfer Difference NMR experiments reveal different interaction patterns with both COXs isoforms that may be related with different orientations of the sulfonamide group in the binding pocket. Despite the moderated inhibitory activities found, this study represents an innovative approach towards COXs inhibitory activity rationalization and to the design of anti-inflammatory drugs.

}, author = {M{\'o}nica S. Estev{\~a}o and Lu{\'\i}sa C. R. Carvalho and Marisa Freitas and Ana Gomes and Viegas, Aldino and Jo{\~a}o Manso and Stefan Erhadrt and Cabrita, Eurico J. and Marques, Maria Manuel B.} } @article {3115, title = {The Prion-like Protein Doppel Enhances Ovine Spermatozoa Fertilizing Ability}, journal = {Reproduction in Domestic Animals}, volume = {47}, year = {2012}, pages = {196-202}, abstract = {

The function of prion-like protein Doppel was suggested to be related to male fertility. In this study, the importance of ovine Doppel polypeptide on spermatozoa capacitation and fertilization was evaluated. After refolding, recombinant Doppel (rDpl) was supplemented with different concentrations (40, 80 or 190 ng/ml) to ovine spermatozoa during the capacitation process. In experiment 1, post-thawed ovine spermatozoa were incubated with different concentrations of rDpl during 1 h for swim-up, and changes in sperm motility, concentration, vigour, viability and capacitation were monitored (10 replicates). In experiment 2, the fertilization ability of post-swim-up spermatozoa incubated as above was tested through heterologous fertilization of bovine in vitro matured oocytes (n = 423, three replicates). Regardless of dosage, rDpl improved (p = 0.03) spermatozoa viability. Sperm individual motility and vigour were the highest (p = 0.04) for the group receiving 190 ng/ml rDpl. Sperm supplemented with the highest doses of rDpl achieved higher (p = 0.02) fertilization rates (56.0 +/- 3.0\%) than control (39.1 +/- 2.2\%) and 40 ng/ml rDpl (39.8 +/- 2.7\%). Preliminary data suggest that Doppel protein may enhance in vitro spermatozoa fertilizing ability.

}, author = {J. Pimenta and Dias, FMV and C. C. Marques and M. C. Baptista and M. I. Vasques and A. E. M. Horta and J. P. Barbas and R. Soares and P. Mesquita and E. Cabrita and Fontes, CMGA and J. A. Prates and R. M. Pereira} } @article {1913, title = {Structural, Physical, and Chemical Modifications Induced by Microwave Heating on Native Agar-like Galactans}, journal = {Jornal of Agricultural and Food Chemistry }, volume = {60}, year = {2012}, pages = {4977-4985}, abstract = {

Native agars from Gracilaria vermiculophylla produced in sustainable aquaculture systems (IMTA) were extracted under conventional (TWE) and microwave (MAE) heating. The optimal extracts from both processes were compared in terms of their properties. The agars{\textquoteright} structure was further investigated through Fourier transform infrared and NMR spectroscopy. Both samples showed a regular structure with an identical backbone, β-D-galactose (G) and 3,6-anhydro-α-L-galactose (LA) units; a considerable degree of methylation was found at C6 of the G units and, to a lesser extent, at C2 of the LA residues. The methylation degree in the G units was lower for MAEopt agar; the sulfate content was also reduced. MAE led to higher agar recoveries with drastic extraction time and solvent volume reductions. Two times lower values of [η] and Mv obtained for the MAEopt sample indicate substantial depolymerization of the polysaccharide backbone; this was reflected in its gelling properties; yet it was clearly appropriate for commercial application in soft-texture food products.

}, author = {Ana M. M. Sousa and Simone Morais and Maria H. Abreu and Rui Pereira and Isabel Sousa-Pinto and Cabrita, Eurico J. and Cristina Delerue-Matos and Maria Pilar Gonca̧lves} } @article {1002, title = {Synthesis of a new pyranoanthocyanin dimer linked through a methyl-methine bridge}, journal = {Tetrahedron Letters}, volume = {52}, number = {23}, year = {2011}, note = {n/a}, month = {JUN 8 2011}, pages = {2957-2960}, abstract = {n/a}, author = {Oliveira, Joana and Mateus, Nuno and Rodriguez-borges, Jose E. and Cabrita, Eurico J. and Silva, Artur M. S. and de Freitas, Victor} } @article {1001, title = {Saturation-Transfer Difference (STD) NMR: A Simple and Fast Method for Ligand Screening and Characterization of Protein Binding}, journal = {Journal of Chemical Education}, volume = {88}, number = {7}, year = {2011}, note = {

n/a

}, month = {JUL 2011}, pages = {990-994}, abstract = {

Saturation transfer difference (STD) NMR has emerged as one of the most popular ligand-based NMR techniques for the study of protein-ligand interactions. The success of this technique is a consequence of its robustness and the fact that it is focused on the signals of the ligand, without any need of processing NMR information about the receptor and only using small quantities of nonlabeled macromolecule. Moreover, the attractiveness of this experiment is also extendable to the classroom. In the context of a practical NMR class, this experiment is ideal to illustrate some fundamental NMR concepts, such as the nuclear Overhauser effect and relaxation in a multidisciplinary context, bridging chemistry and biochemistry with a taste of medicinal chemistry.

We use the readily available human serum albumin (HSA), 6-d,l-methyl-tryptophan (6-CH3-Trp), and 7- d,l-methyl-tryptophan (7-CH3-Trp) to introduce the STD-NMR experiment and to illustrate its applicability for ligand screening, mapping of binding moieties, and determination of the dissociation constant, in a context that can be explored or adapted to the student{\textquoteright}s course level and topic (chemistry or biochemistry). We also cover the most important theoretical aspects of the STD experiment, calling attention to some of its limitations and drawbacks without a complex theoretical approach.

}, url = {http://pubs.acs.org/doi/abs/10.1021/ed101169t}, author = {Viegas, Aldino and Manso, Joao and Nobrega, Franklin L. and Cabrita, Eurico J.} } @article {1087, title = {Binding of ibuprofen, ketorolac and diclofenac to COX-1 and COX-2 studied by saturation transfer difference NMR}, journal = {Journal of Medicinal Chemistry}, volume = {54}, year = {2011}, pages = {8555-8562}, abstract = {

Saturation Transfer Difference-NMR (STD-NMR) spectroscopy has emerged as a powerful screening tool and a straightforward way to study the binding epitopes of active compounds in early stage lead discovery in pharmaceutical research. Here we report the application of STD NMR to characterize the binding of the anti-inflammatory drugs ibuprofen, diclofenac and ketorolac to COX-1 and COX-2. Using well-studied COX inhibitors and by comparing STD signals with crystallographic structures we show that there is a relation between the orientations of ibuprofen and diclofenac in the COX-2 active site and the relative STD responses detected in the NMR experiments. Based on this analysis we propose that ketorolac should bind to the COX-2 active site in similar orientation as that of diclofenac. We also show that the combination of STD NMR with competition experiments constitutes a valuable tool to address the recently proposed behavior of COX-2 as functional heterodimers and complement enzyme activity studies in the effort to rationalize COX inhibition mechanisms.

}, url = {http://pubs.acs.org/doi/abs/10.1021/jm201090k}, author = {Viegas, Aldino and Manso, Joao and Corvo, Marta C. and Marques, M. Manuel B. and Cabrita, Eurico J.} } @article {1009, title = {Application of HR-MAS NMR in the solid-phase synthesis of a glycopeptide using Sieber amide resin}, journal = {Magnetic Resonance in Chemistry}, volume = {48}, number = {4}, year = {2010}, note = {n/a}, month = {APR 2010}, pages = {323-330}, abstract = {n/a}, author = {Carvalho, Luisa R. and Corvo, Marta C. and Enugala, Ramu and Marques, M. Manuel B. and Cabrita, Eurico J.} } @inbook {1040, title = {Ligand based nuclear magnetic resonance screening techniques}, booktitle = {Ligand Macromolecule Interactions in drug discovery, Methods in Molecular Biology}, year = {2010}, pages = {81-100}, publisher = {Humana Press}, organization = {Humana Press}, address = {New York}, author = {A. Viegas and A. L. Macedo and Cabrita, E. J.}, editor = {Ana Cec{\'\i}lia A. Roque} } @article {1010, title = {Ligand-based nuclear magnetic resonance screening techniques.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {572}, year = {2009}, note = {n/a}, month = {2009}, pages = {81-100}, abstract = {n/a}, author = {Viegas, Aldino and Macedo, Anjos L and Cabrita, Eurico J.} } @article {1016, title = {Molecular determinants of ligand specificity in family 11 carbohydrate binding modules - an NMR, X-ray crystallography and computational chemistry approach}, journal = {Febs Journal}, volume = {275}, number = {10}, year = {2008}, note = {n/a}, month = {MAY 2008}, pages = {2524-2535}, abstract = {n/a}, author = {Viegas, Aldino and Bras, Natercia F. and Cerqueira, Nuno M. F. S. A. and Fernandes, Pedro Alexandrino and Prates, Jose A. M. and Fontes, Carlos M. G. A. and Bruix, Marta and Romao, Maria Joao and Carvalho, Ana Luisa and Ramos, Maria Joao and Macedo, Anjos L and Cabrita, Eurico J.} } @article {1023, title = {Residue-specific NH exchange rates studied by NMR diffusion experiments (vol 187, pg 97, 2007)}, journal = {Journal of Magnetic Resonance}, volume = {188}, number = {2}, year = {2007}, note = {n/a}, month = {OCT 2007}, pages = {387-387}, abstract = {n/a}, author = {Brand, Torsten and Cabrita, Eurico J. and Morris, Gareth A. and Guenther, Robert and Hofmann, Hans-Joerg and Berger, Stefan} } @article {1022, title = {Residue-specific NH exchange rates studied by NMR diffusion experiments}, journal = {Journal of Magnetic Resonance}, volume = {187}, number = {1}, year = {2007}, note = {n/a}, month = {JUL 2007}, pages = {97-104}, abstract = {n/a}, author = {Brand, Torsten and Cabrita, Eurico J. and Morris, Gareth A. and Guenther, Robert and Hofmann, Hans-Jorg and Berger, Stefan} } @article {1019, title = {Molecular interactions and CO2-philicity in supercritical CO2. A high-pressure NMR and molecular modeling study of a perfluorinated polymer in scCO(2)}, journal = {Journal of Physical Chemistry B}, volume = {111}, number = {6}, year = {2007}, note = {n/a}, month = {FEB 15 2007}, pages = {1318-1326}, abstract = {n/a}, author = {Temtem, Marcio and Casimiro, Teresa and A. Gil Santos and Macedo, Anjos L and Cabrita, Eurico J. and Aguiar-Ricardo, Ana} } @article {1021, title = {Boron trifluoride catalyzed polymerisation of 2-substituted-2-oxazolines in supercritical carbon dioxide}, journal = {Green Chemistry}, volume = {9}, number = {9}, year = {2007}, note = {n/a}, month = {2007}, pages = {948-953}, abstract = {n/a}, author = {de Macedo, Carlota Veiga and da Silva, Mara Soares and Casimiro, Teresa and Cabrita, Eurico J. and Aguiar-Ricardo, Ana} } @article {1027, title = {Studies on the preparation of 4-ethoxyalkyliden and 4-aminoalkyliden-5(4H)-oxazolones}, journal = {Synthetic Communications}, volume = {33}, number = {8}, year = {2003}, note = {n/a}, month = {2003}, pages = {1285-1299}, abstract = {n/a}, author = {Matos, MRPN and Gois, PMP and Mata, MLEN and Cabrita, E. J. and Afonso, CAM} }