xtal

EUSO2019

Viviana got to meet the Portuguese and Dutch Prime-Ministers!

Together with other PhD students and young post-docs from UCIBIO, in a visit to FCT from the Dutch Prime-Minister.

12th International Conference on Hydrogenases

Maria João Romão giving a plenary talk at the 12th International Conference on Hydrogenases:

“Metal-dependent formate dehydrogenases and the reversible interconversion of CO2 and formate”

Peixoto, D, Malta G, Cruz H, Barroso S, Carvalho AL, Ferreira LM, Branco PS.  2019.  N-Heterocyclic olefin catalysis for the ring opening of cyclic amidine compounds: a pathway to the synthesis of ε-caprolactam and γ-lactam-derived amines, 2019. The Journal of Organic Chemistry. : American Chemical Society AbstractWebsite

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The XTAL at the ESRF SAXS beamline

Francisco Leisico, Diana Ribeiro, Raquel Santos, Raquel Costa & Ana Luísa (taking pictures) in the SAXS beamline, today. All goes well!

Mota, C, Coelho C, Leimkühler S, Garattini E, Terao M, Santos-Silva T, Romão MJ.  2018.  Critical overview on the structure and metabolism of human aldehyde oxidase and its role in pharmacokinetics, 2018. 368:35-59. AbstractWebsite

Aldehyde oxidases are molybdenum and flavin dependent enzymes characterized by a very wide substrate specificity and performing diverse reactions that include oxidations (e.g., aldehydes and aza-heterocycles), hydrolysis of amide bonds, and reductions (e.g., nitro, S-oxides and N-oxides). Oxidation reactions and amide hydrolysis occur at the molybdenum site while the reductions are proposed to occur at the flavin site. AOX activity affects the metabolism of different drugs and xenobiotics, some of which designed to resist other liver metabolizing enzymes (e.g., cytochrome P450 monooxygenase isoenzymes), raising its importance in drug development. This work consists of a comprehensive overview on aldehyde oxidases, concerning the genetic evolution of AOX, its diversity among the human population, the crystal structures available, the known catalytic reactions and the consequences in pre-clinical pharmacokinetic and pharmacodynamic studies. Analysis of the different animal models generally used for pre-clinical trials and comparison between the human (hAOX1), mouse homologs as well as the related xanthine oxidase (XOR) are extensively considered. The data reviewed also include a systematic analysis of representative classes of molecules that are hAOX1 substrates as well as of typical and well characterized hAOX1 inhibitors. The considerations made on the basis of a structural and functional analysis are correlated with reported kinetic and metabolic data for typical classes of drugs, searching for potential structural determinants that may dictate substrate and/or inhibitor specificities.

New review online!

Cristiano Mota, Catarina Coelho, Silke Leimkühler, Enrico Garattini, Mineko Terao, Teresa Santos-Silva, Maria João Romão,
Critical overview on the structure and metabolism of human aldehyde oxidase and its role in pharmacokinetics,
Coordination Chemistry Reviews,
Volume 368,
2018,
Pages 35-59,
ISSN 0010-8545,
https://doi.org/10.1016/j.ccr.2018.04.006.

Carvalho, AL, Santos-Silva T, Romão MJ, Eurico J, Marcelo F.  2018.  {CHAPTER 2 Structural Elucidation of Macromolecules}, sep. Essential Techniques for Medical and Life Scientists: A Guide to Contemporary Methods and Current Applications with the Protocols. :30–91.: BENTHAM SCIENCE PUBLISHERS AbstractWebsite
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A new eBook!

http://www.eurekaselect.com/165742/chapter?fbclid=IwAR3innQHqppf_lJfBuAtgGYJGtVq_RzwQu7WMOeIrWxl26m45cGh38MYklM

Our contribution to the eBook "Essential Techniques for Medical and Life Scientists: A Guide to Contemporary Methods and Current Applications with the Protocols" is now available. Congratulations to all the authors!

Well done, Viviana!

Congratulations to our PhD student Viviana Correia for her 2nd Best Poster Award at the UCIBIO annual meeting! The poster title is "Assessing human microbiota systems for glycan recognition in the gut". Well done, Viviana!

Well done, Francisco!

Francisco Leisico, estudante de doutoramento, apresenta o seu trabalho “Peptidoglycan amidation in Staphylococcus aureus - structure-function studies”

Santarsia, S, Grosso AS, Trovão F, Jiménez-Barbero J, Carvalho AL, Nativi C, Marcelo F.  2018.  Molecular recognition of a Thomsen-Friedenreich antigen mimetic targeting human galectin-3, 2018. ChemMedChem. Aug 9. doi: 10.1002/cmdc.201800525. [Epub ahead of print](ja): Wiley-Blackwell AbstractWebsite

Overexpression of the Thomsen-Friedenreich (TF) antigen in cell membrane proteins occurs in 90% of adenocarcinomas. Additionally, the binding of the TF-antigen to human galectin-3 (Gal-3), also frequently overexpressed in malignancy, promotes cancer progression and metastasis. In this context, structures that interfere with this specific interaction display the potential to prevent cancer metastasis. Herein, a multidisciplinary approach, combining the optimized synthesis of a TF-antigen mimetic with NMR, X-ray crystallography methods and isothermal titration calorimetry assays has been employed to unravel the molecular structural details that govern the Gal-3/TF-mimetic interaction. The TF-mimetic presents a binding affinity for Gal-3 similar to the TF-natural antigen and retains the binding epitope and the bioactive conformation observed for the native antigen. Furthermore, from a thermodynamic perspective a decrease in the enthalpic contribution was observed for the Gal-3/TF-mimetic complex, however this behaviour is compensated by a favourable entropy gain. From a structural perspective, these results establish our TF-mimetic as a scaffold to design multivalent solutions to potentially interfere with Gal-3 aberrant interactions and likely be used to hamper Gal-3-mediated cancer cells adhesion and metastasis.

New paper online!

S. Santarsia, A. S. Grosso, F. Trovão, J. Jiménez-Barbero, A. L. Carvalho, C. Nativi, F. Marcelo, ChemMedChem 2018 13 , 2030.

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