Search Results

You searched for all publications:

with publication states 'Published (Approved)'

Search Again...

These results only include publications that have been reviewed and processed by Diamond Light Source. To also view papers that have not yet been processed click here.

You can use the folder icon under Actions to collate papers as required. You can then click on View Folder in the left-hand navigation to review and/or download your folder.

Exact matches
Related results

2 items found (0 items not approved), displaying all items.1

Instruments / Technical Area	Publication Details	Published	Actions
I02-Macromolecular Crystallography	Inhibitors against fungal cell wall remodeling enzymes Ignacio Delso , Jessika Valero-Gonzalez , Fernando Gomollón-Bel , Jorge Castro-López , Wenxia Fang , Iva Navratilova , Daan M F Van Aalten , Tomás Tejero , Pedro Merino , Ramon Hurtado-Guerrero Chemmedchem 6 DOI: 10.1002/cmdc.201700720 Diamond Proposal Number(s): [10121] Show Abstract ▼ Abstract: Fungal β-1,3-glucan glucanosyltransferases are glucan-remodeling enzymes that play important roles in cell wall integrity, and are essential for the viability of pathogenic fungi and yeasts. As such, they are considered possible drug targets, although inhibitors of this class of enzymes have not yet been reported. Herein we report a multidisciplinary approach based on a structure-guided design using a highly conserved transglycosylase from Sacharomyces cerevisiae, that leads to carbohydrate derivatives with high affinity for Aspergillus fumigatus Gel4. We demonstrate by X-ray crystallography that the compounds bind in the active site of Gas2/Gel4 and interact with the catalytic machinery. The topological analysis of noncovalent interactions demonstrates that the combination of a triazole with positively charged aromatic moieties are important for optimal interactions with Gas2/Gel4 through unusual pyridinium cation–π and face-to-face π–π interactions. The lead compound is capable of inhibiting AfGel4 with an IC50 value of 42 μm.	Dec 2017
I04-Macromolecular Crystallography	Glycomimetics targeting glycosyltransferases: synthetic, computational and structural studies of less-polar conjugates Mattia Ghirardello , Matilde De Las Rivas , Alessandra Lacetera , Ignacio Delso , Erandi Lira-Navarette , Tomás Tejero , Sonsoles Martín-Santamaría , Ramon Hurtado-Guerrero , Pedro Merino Chemistry - A European Journal 22, 7215 - 7224 DOI: 10.1002/chem.201600467 Diamond Proposal Number(s): [10121] Show Abstract ▼ Abstract: The Leloir donors are nucleotide sugars essential for a variety of glycosyltransferases (GTs) involved in the transfer of a carbohydrate to an acceptor substrate, typically a protein or an oligosaccharide. A series of less-polar nucleotide sugar analogues derived from uridine have been prepared by replacing one phosphate unit with an alkyl chain. The methodology is based on the radical hydrophosphonylation of alkenes, which allows coupling of allyl glycosyl compounds with a phosphate unit suitable for conjugation to uridine. Two of these compounds, the GalNAc and galactose derivatives, were further tested on a model GT, such as GalNAc-T2 (an important GT widely distributed in human tissues), to probe that both compounds bound in the medium-high micromolar range. The crystal structure of GalNAc-T2 with the galactose derivative traps the enzyme in an inactive form; this suggests that compounds only containing the β-phosphate could be efficient ligands for the enzyme. Computational studies with GalNAc-T2 corroborate these findings and provide further insights into the mechanism of the catalytic cycle of this family of enzymes.	May 2016

Publications Database

Search Results

You searched for all publications:

Search Again...

Subject Areas (check all that apply) select all

Instruments used to collect data (check all that apply) select all

Collaborations involved (check all that apply) select all

Diamond Offline Facilities used

Relevant Technical Areas (check all that apply) select all

Menu for Anonymous User