Xavier Guillory

Université de Rennes 1 | UR1 · Institut des Sciences Chimiques de Rennes (ISCR) - UMR CNRS 6226

Inositol Requiring Enzyme 1 (IRE1) is a bifunctional serine/threonine kinase and endoribonuclease. It is a major mediator of the Unfolded Protein Response (UPR), which is activated during endoplasmic reticulum (ER) stress. Tumor cells experience ER stress due to adverse microenvironmental cues such as hypoxia or nutrient shortage and high metabolic...

Ganglioside-monosialic acid (GM1) gangliosidosis, a rare autosomal recessive disorder, is frequently caused by deleterious single nucleotide variants (SNVs) in GLB1 gene. These variants result in reduced beta-galactosidase (β-gal) activity, leading to neurodegeneration associated with premature death. Currently, no effective therapy for GM1 ganglio...

The reactivity of eight purified depsides obtained from six european lichens and that display as 2-oxoalkyl chain in ortho-position of the ester bond was explored. These depsides were found to lead to 1H-Isochromen-1-ones, which exhibit a distinctive blue fluorescence at 365 nm, in the presence of a 10% aqueous solution of KOH. A mechanistic explan...

Function-oriented molecular editing of the polycyclic scaffold of securinine led to the preparation of a library of simplified analogs that have been evaluated for their cytotoxicity potential against HCT116 and HL60 human cell lines. Chemical diversity at the C14 position (securinine numbering) was generated through the site-selective γ-iodination...

Inositol Requiring Enzyme 1 (IRE1) is a bifunctional serine/threonine kinase and endoribonuclease. It is a major mediator of the Unfolded Protein Response (UPR), which is activated during endoplasmic reticulum (ER) stress. Tumor cells experience ER stress due to adverse microenvironmental cues such as hypoxia or nutrient shortage and high metabolic...

IRE1α (inositol-requiring enzyme 1 alpha, referred to IRE1 hereafter) is an Endoplasmic Reticulum (ER) resident transmembrane enzyme with cytosolic kinase/RNAse activities. Upon ER stress IRE1 is activated through trans-autophosphorylation and oligomerization, resulting in a conformational change of the RNase domain, thereby promoting two signaling...

IRE1α (inositol requiring enzyme 1 alpha, referred to IRE1 hereafter) is an Endoplasmic Reticulum (ER) resident transmembrane enzyme with cytosolic kinase/RNAse activities. Upon ER stress IRE1 is activated through trans-autophosphorylation and oligomerization, resulting in a conformational change of the RNase domain thereby promoting two signaling...

Rational design of protein–protein interaction (PPI) inhibitors is challenging. Connecting a general supramolecular protein binder with a specific peptidic ligand provides a novel conceptual approach. Thus, lysine-specific molecular tweezers were conjugated to a peptide-based 14–3–3 ligand and produced a strong PPI inhibitor with 100-fold elevated...

The Unfolded Protein response is an adaptive pathway triggered upon alteration of endoplasmic reticulum (ER) homeostasis. It is transduced by three major ER stress sensors, among which the Inositol Requiring Enzyme 1 (IRE1) is the most evolutionarily conserved. IRE1 is an ER-resident type I transmembrane protein exhibiting an ER luminal domain that...

IRE1α (inositol requiring enzyme 1 alpha) is one of the main transducers of the unfolded protein response (UPR). IRE1α plays instrumental protumoral roles in several cancers, and high IRE1α activity has been associated with poorer prognoses. In this context, IRE1α has been identified as a potentially relevant therapeutic target. Pharmacological inh...

Stabilization of protein-protein interactions (PPIs) holds great potential for therapeutic agents, as illustrated by the successful drugs rapamycin and lenalidomide. However, how such interface-binding molecules can be created in a rational, bottom-up manner is a largely unanswered question. We report here how a fragment-based approach can be used...

Previous studies have indicated the presence of defined interactions between oligo or poly(ethylene glycol) (OEG or PEG) and lysine residues. In these interactions, the OEG or PEG residues 'wrap around' the lysine amino group, thereby enabling complexation of the amino group by the ether oxygen residues. The resulting biochemical binding affinity a...

Protein regions that are involved in Protein-Protein Interactions (PPIs) very often display a high degree of intrinsic disorder, which is reduced during the recognition process. A prime example is binding of the rigid 14-3-3 adapter proteins to their numerous partner proteins, whose recognition motifs undergo an extensive disorder-to-order transiti...

For hybrid materials, the relationship between the macroscopic properties and the molecular structures and dynamics at the microscopic between the organic and inorganic components level is crucial. The characterization of these components as well as their reactivity have to be emphasized in order to design and synthesize improved hybrids. We report...

Polysaccharides are among the most abundant macromolecules on Earth. These polymers are easily obtained from various marine resources such as algae, microorganisms and crustacean shells. The structure of these natural carbohydrates is innovative and quite complex. Marine biopolymers represent key scaffolds toward large challenging fields, such as b...

Hydroxypropylmethylcellulose (HPMC) is a biocompatible polymer and a good candidate to make injectable hydrogels. After chemical grafting of silanolate groups under basic conditions, the decrease of pH promotes a self-crosslinked network. Innovative Extra Cellular Matrices (ECMs) are obtained thanks to these particular chemical groups which induce...

We have developed an efficient diastereoselective synthetic route towards a nardosinane sesquiterpene scaffold. The strategy used a key bicyclic diene intermediate 11a, and allowed access to valuable polyoxygenated sesquiterpenes 21 and 22, which may be regarded as analogues of the natural sesquiterpenes laevinol B and fulvol acetate, respectively....