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 I03-Macromolecular Crystallography I04-1-Macromolecular Crystallography (fixed wavelength) I04-Macromolecular Crystallography	Structure-guided discovery of potent and selective DYRK1A inhibitors Csaba Weber , Melinda Sipos , Attila Paczal , Balazs Balint , Vilibald Kun , Nicolas Foloppe , Pawel Dokurno , Andrew J. Massey , David Lee Walmsley , Roderick E. Hubbard , James Murray , Karen Benwell , Thomas Edmonds , Didier Demarles , Alain Bruno , Mike Burbridge , Francisco Cruzalegui , Andras Kotschy Journal Of Medicinal Chemistry DOI: 10.1021/acs.jmedchem.1c00023 Diamond Proposal Number(s): [1857, 2103] Show Abstract ▼ Abstract: The kinase DYRK1A is an attractive target for drug discovery programs due to its implication in multiple diseases. Through a fragment screen, we identified a simple biaryl compound that is bound to the DYRK1A ATP site with very high efficiency, although with limited selectivity. Structure-guided optimization cycles enabled us to convert this fragment hit into potent and selective DYRK1A inhibitors. Exploiting the structural differences in DYRK1A and its close homologue DYRK2, we were able to fine-tune the selectivity of our inhibitors. Our best compounds potently inhibited DYRK1A in the cell culture and in vivo and demonstrated drug-like properties. The inhibition of DYRK1A in vivo translated into dose-dependent tumor growth inhibition in a model of ovarian carcinoma.	May 2021
B24-Cryo Soft X-ray Tomography	Supramolecular attack particles are autonomous killing entities released from cytotoxic T cells S. Balint , S. Müller , R. Fischer , B. M. Kessler , M. Harkiolaki , S. Valitutti , M. L. Dustin Science DOI: 10.1126/science.aay9207 Diamond Proposal Number(s): [23000] Show Abstract ▼ Abstract: Cytotoxic T lymphocytes (CTLs) kill infected and cancerous cells. We detected transfer of cytotoxic multiprotein complexes from CTLs to target cells, termed supramolecular attack particles (SMAPs). SMAPs were rapidly released from CTLs and were autonomously cytotoxic. Mass spectrometry, immunochemical analysis and CRISPR editing identified a C-terminal fragment of thrombospondin-1 as an unexpected SMAP component that contributed to target killing. Direct stochastic optical reconstruction microscopy resolved a cytotoxic core surrounded by a thrombospondin-1 shell of ~120 nm diameter. Cryo-soft x-ray tomography analysis revealed that SMAPs had a carbon-dense shell and were stored in multicore granules. We propose that SMAPs are autonomous extracellular killing entities that deliver cytotoxic cargo based on specificity of shell components.	May 2020

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