Chemical Biology Metal Catalysis

Our Aims

Generation, training and transfer of knowledge

Development of creative and groundbreaking
research at the interface of Chemistry, Biology and Medicine.

Education of researchers in order they become
future leaders of academic or industrial projects.

Transferring of knowledge to Society in order
to propel economical and social progress

European Research Council Santiago de Compostela University Campus Vida CIQUS - Centro Singular de Investigación en Química Biológica y Materiales Moleculares
Latest News
Media Library

Our new paper at Bioorg. Chem. in colaboration with Prof. Mollica is already on-line

03/22/2021
So happy to share our last collaboration with Mollica's group is already published in the Bioorganic Chemistry journal

We are very glad to announce here that our research article at Bioorg. Chem. in collaboration with Mollica's group, entitled "A novel β-hairpin peptide derived from the ARC repressor selectively interacts with the major groove of B-DNA" and authored by A. Stefanucci, J. Amato, D. Brancaccio, B. Pagano, A. Randazzo, F. Santoro, L. Mayol, S. Learte, J. Rodríguez, J. L. Mascareñas, E. Novellino, A. Carotenuto and A. Mollica, has been accepted and it's already available through the journal website.

Abstract: Transcription factors (TFs) have a remarkable role in the homeostasis of the organisms and there is a growing interest in how they recognize and interact with specific DNA sequences. TFs recognize DNA using a variety of structural motifs. Among those, the ribbon-helix-helix (RHH) proteins, exemplified by the MetJ and ARC repressors, form dimers that insert antiparallel β-sheets into the major groove of DNA. A great chemical challenge consists of using the principles of DNA recognition by TFs to design minimized peptides that maintain the DNA affinity and specificity characteristics of the natural counterparts. In this context, a peptide mimic of an antiparallel β-sheet is very attractive since it can be obtained by a single peptide chain folding in a β-hairpin structure and can be as short as 14 amino acids or less. Herein, we designed eight linear and two cyclic dodeca-peptides endowed with β-hairpins. Their DNA binding properties have been investigated using fluorescence spectroscopy together with the conformational analysis through circular dichroism and solution NMR. We found that one of our peptides, peptide 6, is able to bind DNA, albeit without sequence selectivity. Notably, it shows a topological selectivity for the major groove of the DNA which is the interaction site of ARC and many other DNA-binding proteins. Moreover, we found that a type I’ β-hairpin folding pattern is a favorite peptide structure for interaction with the B-DNA major groove. Peptide 6 is a valuable lead compound for the development of novel analogs with sequence selectivity.

See limited-time downloadable version at https://authors.elsevier.com/c/1cqckAHs8WTkL



External link: https://www.sciencedirect.com/science/article/abs/pii/S0045206821002133

Our last paper at 'The Journal of the American Chemical Society' is available as Article ASAP

03/03/2021
We are very glad to announce our first 2021 J. Am. Chem. Soc. paper is already on-line

We are very happy to share here that our research article at J. Am. Chem. Soc., entitled "Kinetic Resolution of Allyltriflamides through a Pd-Catalyzed C–H Functionalization with Allenes: Asymmetric Assembly of Tetrahydropyridines" and authored by J. M. González, B. Cendón, J. L. Mascarenas and M. Gulías, has been accepted and it's already available through the journal website.


Abstract: Enantioenriched, six-membered azacycles are essential structural motifs in many products of pharmaceutical or agrochemical interest. Here we report a simple and practical method for enantioselective assembly of tetrahydropyridines, which is paired to a kinetic resolution of α-branched allyltriflamides. The reaction consists of a formal (4+2) cycloaddition between the allylamine derivatives and allenes and is initiated by a palladium(II)-catalyzed C–H activation process. Both the chiral allylamide precursors and the tetrahydropyridine adducts were successfully obtained in high yields, with excellent enantioselectivity (up to 99% ee) and selectivity values of up to 127.






External link: https://pubs.acs.org/doi/10.1021/jacs.1c01929

Our first publication for 2021 is on-line

01/20/2021
Pleased to announce our most recent Angew. Chem. Int. Ed. manuscript has been accepted, and it's already available

We are very happy to share here that our research article at Angew. Chem. Int. Ed., entitled "Highly Enantioselective Cobalt‐Catalyzed (3 + 2) Cycloadditions of Alkynylidenecyclopropanes" and authored by E. Da Concepción, I. Fernández, J. L. Mascarenas and F. López, has been accepted and it's already available through the journal website.

Abstract: Low‐valent cobalt complexes equipped with chiral ligands can efficiently promote highly enantioselective (3+2) cycloadditions of alkyne‐tethered alkylidenecyclopropanes. The annulation allows to assemble bicyclic systems containing five‐membered rings in good yields and with excellent enantiomeric ratios. We also present a mechanistic discussion based on experimental and computational data, which support the involvement of Co(I)/Co(III) catalytic cycles




External link: https://onlinelibrary.wiley.com/doi/10.1002/anie.202015202

One of our last publications at ACIE is getting plenty of attention

09/29/2020
This VIP (Very Important Paper) at Angew. Chem. Int. Ed. shows a very complex chemical reaction run at the living cell for the very first time

This work, published by the beginning of July at Angew. Chem. Int. Ed. and authored by Joan Miguel, María Tomás and José Luis Mascareñas, has been considered as a Very Important Paper by the reviewers.


See some news at:


External link: https://onlinelibrary.wiley.com/toc/15213773/2020/59/40

Synthetic models in Chemical Biology

04/10/2021
Workshop on Nanomedicine 2012. Prof. Mascareñas, ERC - Advanced Grant METBIOCAT, explains his research lines in the chemical biology field.
DNA is the key macromolecule used by nature to store the genetic information, therefore containing all the instructions that control the day-to-day function of cells. As such, it has been a traditional target for the development of different type of drugs, particularly anticancer agents. These drugs include alkylating agents, like cis-platinum and derivatives, and non-covalent binders like the anthracyclines, which interact to DNA by intercalation between base pairs. There are other types of cytotoxic non-covalent DNA binders, like distamycin or propamidine, which interact to DNA by insertion in the minor groove.

We have been interested in this latter type of molecules, because they are sequence selective and therefore provide for molecular engineering of site-specific DNA-promoted processes. In particular, we have designed and synthesized a number of variants of propamidine that work as sequence specific DNA optical sensors, or as light-activated prodrugs.

Some of the knowledge acquired in the studies of light-promoted processes has been extended to area of DNA-protein interactions. In particular, we have developed a chemical approach to control the DNA interaction of synthetic mimics of transcription factors, and expect that the tactic can be used in the future to regulate processes of gene expression.
Part of our work in this area is also focused to the construction of optical sensors that can detect minute amounts of transcription factors considered as oncogenic biomarkers, like the bZIP protein Jun.

Meet our team

José Luis Mascareñas, PhD leads this team of researchers. Find out more about him and the rest of the team in our Group members section.

Group Members

Join Us

We are always looking forward to welcoming exceptional candidates into our research Group. Please visit our Opportunities section or send us your cv.

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Living and working in
Santiago de Compostela

Are you new to the city and its University?
We have gathered some facts and figures you may find interesting.

15ºC

Annual mean temperature. The humid oceanic climate guarantees mild weather throughout the year.

33,000

Students attend the University. With the city population around 100,000.

500

Year old University. Currently imparting more than 60 degrees.

Connected

Santiago is well connected, having its own international airport, train station, etc.

Heritage

Amongst many awards, Santiago was declared World Heritage City by UNESCO in 1985.

Galicia

Santiago de Compostela is the capital of Galicia de most Nortwestern region of Spain.

Transport

Public transport is available in order to get around the city, which is also conveniently located to visit other sites in Galicia.

Language

Spanish and Galician are the two official languages of Galicia. Your work will be carried out in English.

Resources

Official websites:
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