Jessica Rodriguez

• PostDoc Position at Université Toulouse III - Paul Sabatier

Background Previous studies by our group have shown that oxidative phosphorylation (OXPHOS) is the main pathway by which pancreatic cancer stem cells (CSCs) meet their energetic requirements; therefore, OXPHOS represents an Achille’s heel of these highly tumorigenic cells. Unfortunately, therapies that target OXPHOS in CSCs are lacking. Methods Th...

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 valid...

Herein, we describe an approach for the on-demand disassembly of dimeric peptides using a palladium-mediated cleavage of a designed self-immolative linker. The utility of the strategy is demonstrated for the case of dimeric basic regions of bZIP transcription factors. While the dimer binds designed DNA sequences with good affinities, the peptide-DN...

The hemilabile Ad2P(o-C6H4)NMe2 ligand promotes fast, quantitative and irreversible oxidative addition of alkynyl and vinyl iodides to gold. The reaction is general. It works with a broad range of substrates of various electronic bias and steric demand, and proceeds with complete retention of stereochemistry from Z and E vinyl iodides. Both alkynyl...

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 tha...

ConspectusDNA is the molecule responsible for the storage and transmission of the genetic information in living organisms. The expression of this information is highly regulated. In eukaryotes, it is achieved mainly at the transcription level thanks to specialized proteins called transcription factors (TFs) that recognize specific DNA sequences, th...

Here, we report the application of surface-enhanced Raman scattering (SERS) spectroscopy as a rapid and practical tool for assessing the formation of coordinative adducts between nucleic acid guanines and ruthenium polypyridyl reagents. The technology provides a practical approach for the wash-free and quick identification of nucleic acid structure...

Over the past several years, transition‐metal‐mediated chemical reactions have been increasingly used for chemo‐ and regioselective modification of biomolecules. In this Minireview, by J. Rodríguez and M. Martínez‐Calvo on page 9792 ff., the recent developments in this rapidly evolving field have been summarized. While most biomolecule functionaliz...

The site‐selective modification of biomolecules has grown spectacularly in recent years. The presence of a large number of functional groups in a biomolecule makes its chemo‐ and regioselective modification a challenging goal. In this context, transition‐metal‐mediated reactions are emerging as a powerful tool owing to their unique reactivity and g...

The nickel(II)‐mediated self‐assembly of a multimeric DNA binder is described. The binder is composed of two metal‐chelating peptides derived from a bZIP transcription factor (brHis2) and one short AT‐hook domain equipped with two bipyridine ligands (HkBpy2). These peptides reversibly assemble in the presence of NiII ions at selected DNA sequences...

Gold(III) π‐complexes have been authenticated recently with alkenes, alkynes, and arenes. The key importance of PdII π‐allyl complexes in organometallic chemistry (Tsuji–Trost reaction) prompted us to explore gold(III) π‐allyl complexes, which have remained elusive so far. The (P,C)AuIII(allyl) and (methallyl) complexes 3 and 3′ were readily prepar...

Cycling between Au(I) and Au(III) is challenging so that gold-catalyzed cross-couplings are rare. The (MeDalphos)AuCl complex, which we showed prone to undergo oxidative addition, is reported here to efficiently catalyze the C‒N coupling of aryl iodides and amines. The transformation does not require external oxidant nor directing group. It is robu...

Goldrausch: Die π‐Koordination von Allylgruppen zu (P,C)‐koordiniertem Gold(III) und ihre Fähigkeit, nucleophile Additionen anzutreiben, wurden authentifiziert. Spektroskopische und kristallographische Analysen in Kombination mit detaillierten DFT‐Rechnungen stützen das Bild einer gespannten, quasi‐symmetrischen η³‐Koordination der Allylgruppe. Ab...

The ability of the hemilabile (P,N) MeDalphos ligand to trigger oxidative addition of iodoarenes to gold has been thoroughly studied. Competition experiments and Hammett correlations substantiate a clear preference of gold for electron-enriched substrates both in stoichiometric oxidative addition reactions and in catalytic C‒C cross-coupling with 1...

Discrete palladium (II) complexes featuring purposely designed phosphine ligands can promote depropargylation and deallylation reactions in cell lysates. The performance of these complexes is superior to that of other palladium sources, which apparently are rapidly deactivated in such hostile complex media. This good balance between reactiv-ity and...

Obtaining artificial proteins that mimic the DNA binding properties of natural transcription factors could open new ways of manipulating gene expression at will. In this context it is particularly interesting to develop simple synthetic systems. Inspired by the modularity of natural transcription factors, we have designed synthetic miniproteins tha...

We describe an approach to regulate the cellular uptake of small gold nanoparticles using supramolecular chemistry. The strategy relies on the functionalization of AuNPs with negatively charged pyranines, which largely hamper their penetration in cells. Cellular uptake can be activated in situ through the addition of cationic covalent cages that sp...

Square way to heaven: As a result of their square-planar geometry, the reactive site of gold(III) complexes is much closer to the ancillary ligands. This offers new perspectives in asymmetric catalysis, as recently evidenced by the groups of Wong and Toste with well-defined chiral complexes.

Asymmetrisch im Quadrat: Aufgrund ihrer quadratisch-planaren Geometrie befindet sich das reaktive Zentrum von Gold(III)-Komplexen in engerer Nähe zu den Hilfsliganden. Daraus folgen neue Perspektiven für die asymmetrische Katalyse, wie kürzlich die Arbeitsgruppen von Wong und Toste mit wohldefinierten chiralen Komplexen demonstrieren konnten (siehe...

A fragment of the DNA basic region (br) of the GCN4 bZIP transcription factor has been modified to include two His residues at designed i, and i+4 positions of its N-terminus. The resulting monomeric peptide (brHis2) does not bind to its consensus target DNA site (5’-GTCAT-3’). However, addition of cis-Pd(en)Cl2 promotes a high-affinity interaction...

The cell internalization of designed oligoarginine peptides equipped with six glutamic acid residues and an anionic pyranine at the N-terminus is triggered upon addition of a supramolecular host. This host binds specifically to the pyranine moiety, enabling the complex to traverse the cell membrane. Interestingly, none of the components, neither th...

Supplementary

Guanine quadruplexes (GQs) are compact four-stranded DNA structures that play a key role in the control of a variety of biological processes, including gene transcription. Bulky ruthenium complexes featuring a bipyridine, a terpyridine, and one exchangeable ligand ([Ru(terpy)(bpy)X](n+) ) are able to metalate exposed guanines present in the GQ of t...

Guanine quadruplexes (GQs) are compact four-stranded DNA structures that play a key role in the control of a variety of biological processes, including gene transcription. Bulky ruthenium complexes featuring a bipyridine, a terpyridine, and one exchangeable ligand ([Ru(terpy)(bpy)X]n+) are able to metalate exposed guanines present in the GQ of the...

We describe the synthesis of designed peptidic modules that self-assemble in specific DNA sequences of 12 base pairs in the presence of Ni(II) salts. The modules consist of modified fragments of transcription factors that have been appropriately engineered to include metal-chelating His and bipyridine ligands.

We report the rational design of a DNA-binding peptide construct composed of the DNA-contacting regions of two transcription factors (GCN4 and GAGA) linked through an AT-hook DNA anchor. The resulting chimera, which represents a new, non-natural DNA binding motif, binds with high affinity and selectivity to a long composite sequence of 13 base pair...

We report the development of chimeric DNA binding peptides comprised of the DNA binding fragment of natural transcription factors (basic region of a bZIP protein or a monomeric zinc finger module) and an AT-Hook peptide motif. The resulting peptide conjugates display high DNA affinity and excellent sequence selectivity. Furthermore, the the AT-Hook...

We report the construction of conjugates between three variants of the helix 3 region of a Q50K engrailed homeodomain and bisbenzamidine minor-groove DNA binders. The hybrid featuring the sequence of the native protein failed to bind to DNA; however, modifications that increased the α-helical folding propensity of the peptide allowed specific DNA b...

We report the selective modification of cysteine residues engineered in peptides that have two additional cysteine residues as part of a Cys2His2 zinc finger motif. The chemoselective modification is achieved, thanks to the protecting effect exerted by the zinc cation upon coordination with the native cysteines and histidines of the zinc-finger fol...