Goodbye Jose M. Glez and Edu Da Concepción
07/31/2023
Please find below all relevant news regarding our Group.
Click on a headline in order to read the full article.
External link: https://www.usc.es/ciqus/en/news/ciqus-scientific-director-jose-luis-mascarenas-new-numerary-member-royal-academy-pharmacy
Abstract: We report the modelling of the DNA complex of an artificial miniprotein composed of two zinc finger modules and an AT-hook linking peptide. The computational study provides for the first time a structural view of these types of complexes, dissecting interactions that are key to modulate their stability. The relevance of these interactions was validated experimentally. These results confirm the potential of this type of computational approach for studying peptide–DNA complexes and suggest that they could be very useful for the rational design of non-natural, DNA binding miniproteins.
External link: https://pubs.rsc.org/en/content/articlelanding/2023/CB/D3CB00053B
Abstract: Cationic cyclopentadienyl Ru(II) catalysts can efficiently promote mild intermolecular alkyne-alkene couplings in aqueous media, even in the presence of different biomolecular components, and in complex media like DMEM. The method can also be used for the derivatization of aminoacids and peptides, therefore proposing a new way to label biomolecules with external tags. This C-C bond-forming reaction, based on simple alkene and alkyne reactants, can now be added to the toolbox of bioorthogonal reactions promoted by transition metal catalysts.
External link: https://pubs.rsc.org/en/Content/ArticleLanding/2023/SC/D3SC01254A
Abstract: The ability to perform 'new-to-nature' chemical reactions within living cells and organisms is transforming the way in which scientists interrogate and/or manipulate biological processes. In recent years, the toolbox of bioorthogonal and cell-compatible reactions has been enriched with the incorporation of transition metal-mediated processes. Whereas the efficiency of these reactions is still low, the breadth and generality of organometallic catalysis promises to significantly impact the field of bioorthogonal chemistry. Particularly attractive is the possibility of using organometallic catalysis for performing bond-forming, synthetically relevant reactions, as this could allow assembly of biorelevant products at specific biological sites.
External link: https://www.sciencedirect.com/science/article/pii/S2589597423000916
External link: https://twitter.com/angew_chem/status/1628756815558111233?t=hGIZNltqhjtCr0n2JAAX4A&s=19
Abstract: Recent years have witnessed a considerable progress in research aimed at merging transition metal catalysis with chemical and cell biology. Therefore, a crescent number of metal-catalyzed transformations have been shown compatible with biological media and even with living settings. Of the different transition metals used to build these biocompatible catalysts, ruthenium has demonstrated to be particularly powerful, in part because the resulting complexes exhibit a very good balance between reactivity and biological stability. Indeed, ruthenium complexes have demonstrated utility to promote a great variety of reactions in biologically relevant contexts, from deprotection and redox processes to cycloadditions or photocatalytic transformations. Many of these reactions may enable the development of new type of biological tools and pharmacological strategies.
External link: https://onlinelibrary.wiley.com/doi/abs/10.1002/hlca.202300001
Editorial Board Member Professor Andy Wilson highlights Controlling oncogenic KRAS signaling pathways with a Palladium-responsive peptide by Eugenio Vázquez, José Mascareñas and colleagues (https://doi.org/10.1038/s42004-022-00691-7). “This is a really nice interdisciplinary manuscript at the interface of chemical biology and supramolecular chemistry; it is beautifully presented and focuses as its centrepiece on the ability to reversibly nucleate an α-helix through coordination of histidine residues placed at the i and i + 4 positions in the peptide sequence with cis-protected palladium. The method is applied to target a key protein–protein interaction that activates the MAP kinase pathway—the interaction between RAS and its activator SOS1. RAS frequently misfunctions in human cancers and has become an important target for development of molecular therapeutics. What is particularly impressive about the paper is the broad range of experiments used; both circular dichroism and NMR are used for structure elucidation of the stimuli responsive peptide, then direct fluorescence anisotropy binding and nucleotide exchange assays used to characterize interaction with RAS and inhibition of the SOS1/RAS interaction, and then finally cell uptake is monitored alongside effects on the MAPK kinase cascade through inhibition of ERK phosphorylation. A further important concept is introduced, specifically that whilst the palladium clip induces some helicity in the peptide, this is only partial, but the effect is proposed to be sufficient to promote RAS binding (relative to the peptide in the absence of palladium) through a bind and fold mechanism similar to that through which many intrinsically disordered proteins operate. Overall, the paper comprises rigorous experimentation and introduces several new concepts. Given the widespread interest in the development of constrained peptides as protein–protein interaction inhibitors, this represents an important advance for the area of constrained peptides.”
External link: https://www.nature.com/collections/efiidgdgfa
Abstract: Iridium-catalyzed borylations of aromatic C–H bonds are highly attractive transformations owing to the diversification possibilities offered by the resulting boronates. These transformations are best carried out using bidentate bipyridine or phenanthroline ligands, and tend to be governed by steric factors, therefore resulting in the competitive functionalization of meta and/or para positions. We have now discovered that a subtle change in the bipyridine ligand, namely, the introduction of a CF3 substituent at position 5, enables a complete alteration of regioselectivity in the borylation of aromatic amides, providing for the synthesis of a wide variety of ortho-borylated derivatives. Importantly, thorough computational studies suggest that the exquisite regio- and chemoselectivity stems from unusual outer-sphere interactions between the amide group of the substrate and the CF3–substituted aryl ring of the bipyridine ligand.
External link: https://onlinelibrary.wiley.com/doi/10.1002/anie.202214510