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1,463 items found (0 items not approved), displaying 1 to 10.[First/Prev] 1, 2, 3, 4, 5, 6, 7, 8 [Next/Last]

Instruments / Technical Area	Publication Details	Published
I04-Macromolecular Crystallography	Use of direct-to-biology strategies for the discovery of 2′-deoxynucleoside 5′-monophosphate N-glycosidase (DNPH1) PROTACs Niall A. Anderson , Bernard Barlaam , Argyrides Argyrou , Peter C. Astles , Hanna Bruss , Elaine B. Cadogan , Luca Carlino , Luz Alonso-Crisostomo , Gavin W. Collie , Alex J. Edwards , Anastasiia Gryniukova , James Hall , Kunzah Jamal , Joshua Kent , Linda Kitching , Christopher Kourra , Carolyn Lam , Alexander G. Milbradt , Jenni Nikkilä , Sarah Northall , Mark J. O’connor , Jeroen Overman , Claudio Pathe , Wendy Savory , Daniel Slade , Jonathan A. Spencer , Darren Stead , Christopher J. Stubbs , Benjamin C. Whitehurst , Sabrina Winfield Journal Of Medical Chemistry 68 DOI: 10.1021/acs.jmedchem.5c02337 Diamond Proposal Number(s): [20015] Show Abstract ▼ Abstract: 2′-Deoxynucleoside 5′-monophosphate N-glycosidase (DNPH1) has emerged as an attractive target for cancer therapeutics exploiting DNA damage response pathways, yet chemical degraders for interrogating DNPH1 biology are lacking. We report the accelerated discovery of potent DNPH1 PROTACs using a direct-to-biology synthesis and screening platform. We employed miniaturized, array-based chemistry to generate a broad library of quinazoline-based PROTACs capable of recruiting a variety of different E3 ligases. Screening crude reaction mixtures in a cellular degradation assay enabled rapid identification of multiple nanomolar DNPH1 PROTACs, exemplified by compound 59, which achieved near-complete DNPH1 degradation and demonstrated strong functional activity in BRCA1 mutant cell lines. Mechanistic studies confirmed selective, proteasome- and VHL-dependent protein knockdown and recapitulation of phenotypic outcomes observed with DNPH1 genetic loss, including sensitization to hmdU treatment. Our findings highlight the power of D2B methodology to streamline PROTAC development and establish quinazoline-based degraders as robust chemical tools to advance DNPH1-targeted cancer research.	Nov 2025
labSAXS-Offline SAXS and Sample Environment Development	Stepwise π-extension of double [5]helicene diimides to planar nanographene diimides Vikas Sharma , Jacob Isaac , Anmol Thanai , Kieran Richards , Daniel T. W. Toolan , George F. S. Whitehead , Emrys W. Evans , Ashok Keerthi Communications Chemistry 8 DOI: 10.1038/s42004-025-01743-4 Diamond Proposal Number(s): [40538] Open Access Show Abstract ▼ Abstract: A facile, stepwise synthetic route has been developed to access symmetric double [5]helicene diimides and their planar nanographene diimide counterparts via a C-shaped asymmetric [5]helicene. The synthetic strategy employs benzannulation and Scholl reaction methodologies to achieve progressive π-extension, yielding a new class of n-type rylene diimides with reversible redox characteristics. These helical and planar diimides exhibit variable crosswise π-conjugation and structural tunability, resulting in emission wavelengths that can be tailored alongside enhanced photoluminescence quantum yields—from 12% for the S-shaped diimide, to 57% for the C-shaped intermediate, and up to 63% for the fully planar nanographene diimide. Such properties make them promising candidates for quantum photonics, particularly as single-photon emitters. Photophysical properties, including time-resolved photoluminescence and transient absorption spectroscopy, reveal correlations between molecular structure, exciton dynamics, and emission behaviour. Notably, these helical rylene diimides demonstrate high photoluminescence efficiency in the solid state, reaching up to 32%, positioning them as strong contenders for next-generation optoelectronic devices.	Nov 2025
I04-Macromolecular Crystallography	Biocatalytic activation of sulfur heteroaromatics facilitates dearomatizing cross-couplings to set stereogenic centers or axes Anthony P. Green , David J. Procter , Órla Conboy , Emily Q. Rushworth , Christopher J. Taylor , Colin Levy , Mary Ortmayer , George F. S. Whitehead , Andy Yen , Ciro Roman Journal Of The American Chemical Society DOI: 10.1021/jacs.5c16261 Diamond Proposal Number(s): [31850] Show Abstract ▼ Abstract: The enantioselective manipulation of abundant flat (hetero)aromatic building blocks through either dearomatization, to establish new stereocenters, or cross-coupling, to construct a stereogenic axis, is an attractive means to generate three-dimensional molecular architectures. By merging the selectivity of engineered biocatalysts with the versatility of chemical synthesis, we establish a new platform for the metal-free enantioselective manipulation of sulfur-containing heteroaromatics, allowing either point or axial chirality to be set. The key to this approach is our ability to leverage the prochirality of sulfur heteroarenes; biocatalytic oxidation of benzothiophenes “switches on” reactivity and establishes a sulfur stereocenter that directs the stereochemical course of subsequent cross-couplings with non-prefunctionalized partners. Exploiting a previously unexplored mechanism, either point-to-point or point-to-axial chirality transfer from sulfur selectively delivers two different sets of chiral molecules. Enzyme evolution is used to convert a wild-type oxygenase into an efficient and selective engineered S-oxygenase capable of furnishing enantiopure benzothiophene S-oxides─little-known sulfoxides whose configurational stability we map out. Our integrated chemoenzymatic approach provides a blueprint for unlocking the potential of sulfur chirality, lying dormant in important heterocycles, to direct transformations that deliver diverse enantioenriched products.	Nov 2025
I15-1-X-ray Pair Distribution Function (XPDF)	Luminescent chiral molecular glasses by melt-quenching enantiopure BINAP Nuttaporn Krittametaporn , Philipp Ralle , Dorothea Dierks , Christian Nelle , Suresh K. Vasa , Pascal Kolodzeiski , Rasmus Linser , Andreas Steffen , Sebastian Henke Advanced Science DOI: 10.1002/advs.202518879 Diamond Proposal Number(s): [36120] Open Access Show Abstract ▼ Abstract: Chiral organic glasses combine unique optical properties with the processing advantages of amorphous solids. Here, melt-quenching as a strategy for preparing optically active glasses from enantiopure BINAP (2,2′-bis(diphenylphosphino)-1,1′-binaphthyl), a pivotal ligand in asymmetric catalysis and for luminescent metal complexes is demonstrated. Thermal characterization reveals that only R-BINAP and S-BINAP, not rac-BINAP, form molecular glasses with glass transition temperatures near 100 °C. Pair distribution function analysis and circular dichroism confirm the retention of local structure and homochirality despite the loss of long-range order. Remarkably, the glassy state has a beneficial influence on the molecular optoelectronic properties relative to the crystalline state, resulting in an increase of the radiative rate constant by ≈30%, attributed to more favourable Franck-Condon factors. In addition, a highly unusual simultaneous enhancement of circularly polarized luminescence (CPL) by nearly an order of magnitude is observed, achieving dissymmetry factors \|glum\| approaching 10−2 that are competitive with the top-performing purely organic molecular chiral emitters reported to date. These findings establish melt-quenched chiral molecular glasses as promising platforms for advanced optoelectronic and photonic materials, combining exceptional chiroptical properties, strong luminescence, and processability without the constraints of crystallinity.	Nov 2025
I03-Macromolecular Crystallography I04-Macromolecular Crystallography I24-Microfocus Macromolecular Crystallography	An asymmetric hydrogen atom transferase with an abiological thiophenol cofactor Hui Cao , Thomas R. Ward , Kailin Zhang , Vladimir Gorbachev , Tobias Vornholt , Kun Yu , Dongping Chen Journal Of The American Chemical Society DOI: 10.1021/jacs.5c12516 Show Abstract ▼ Abstract: Biocatalytic hydrogen atom transfer (HAT) holds the potential to help address some long-standing challenges in organic synthesis. Although several families of enzymes rely on cysteine to perform HAT, these enzymes are rather impractical for synthetic purposes. To circumvent possible side reactions associated with cysteinyl radicals, we report herein artificial hydrogen atom transferases (AHATases) with an abiological thiophenol cofactor, capitalizing on biotin–streptavidin technology. Chemogenetic optimization afforded an AHATase with good reactivity and high enantioselectivity (er up to 93:7) for the photoinduced radical hydroamination of alkenes. Crystal structures suggest that aromatic-sulfur interactions are key contributing factors to cofactor anchoring and enantioinduction. Mechanistic studies support H atom abstraction and donation processes, both of which are catalyzed by the AHATase. Our work highlights the synthetic potential of thiol-based biocatalytic HAT and expands the repertoire of HAT biocatalysis.	Nov 2025
	The UV photoinduced ring-closing reaction of cyclopentadiene probed with ultrafast electron diffraction Jackson Lederer , Martin Centurion , Lauren Bertram , Lisa Huang , Surjendu Bhattacharyya , Sebastien Boutet , Xinxin Cheng , Stuart W. Crane , Robert J. England , Martin Graßl , Lauren Heald , Fuhao Ji , Patrick Kramer , Huynh Van Sa Lam , Kirk Larsen , Cuong Le , Ming-Fu Li , Yusong Liu , Kenneth Lopata , Mike Minitti , Sri Bhavya Muvva , J. Pedro F. Nunes , Zane Phelps , Sharon Santhamma Philip , Krishna Khakurel , Alexander Hume Reid , Daniel Rolles , Artem Rudenko , Sajib Kumar Saha , John Searles , Xiaozhe Shen , Jiayue Wang , Stephen P. Weathersby , Peter M. Weber , Thomas J. A. Wolf , Yanwei Xiong , Tianzhe Xu , Longteng Yun , Haoran Zhao , Adam Kirrander , Jie Yang The Journal Of Physical Chemistry A DOI: 10.1021/acs.jpca.5c05681 Show Abstract ▼ Abstract: Conjugated cyclic organic molecules are common across many fields such as pharmaceuticals, are naturally occurring in biological systems, and are used in synthetic materials. One particular area of interest from a photochemical point of view is the formation of highly strained cyclic organics. We investigate the photoinduced reaction of cyclopentadiene, a five-membered organic ring molecule, which can form strained three and four carbon rings after photoexcitation with UV light, with the gas-phase ultrafast electron diffraction instrument at the SLAC MeV-UED facility. Electron diffraction offers a direct probe sensitive to the nuclear geometry during the reaction, allowing for the determination of the distribution of products formed following photoexcitation. We observe the simultaneous formation of the highly strained ring-closed bicyclo[2.1.0]pentene and vibrationally hot cyclopentadiene within the temporal resolution of the experiment and determine the relative yield of all reaction products. The experimental results are in good agreement with the predictions of trajectory simulations.	Nov 2025
B18-Core EXAFS	Selective reductive amination of carbonyls to primary amines under ambient conditions over Rh/MFM-300(Cr) Qingqing Mei , Wenyuan Huang , Longfei Lin , Xue Han , Shaojun Xu , Bing An , Svemir Rudic , Rongsheng Cai , Sarah J. Haigh , Buxing Han , Martin Schroeder , Sihai Yang Angewandte Chemie International Edition DOI: 10.1002/anie.202519641 Diamond Proposal Number(s): [36450] Open Access Show Abstract ▼ Abstract: The synthesis of organic amines via reductive amination of biomass-derived carbonyl compounds is an important target for sustainable chemical industries. The control of selectivity for the formation of primary amines versus secondary amines is challenging, and high temperature and pressures using H2 are required to generate the desired selectivity. Herein, we report the highly selective reductive amination of a broad range of aldehydes and ketones by NH3 and H2 over Rh/MFM-300(Cr) to form primary amines with a selectivity of up to 99% under ambient conditions. Inelastic neutron scattering reveals that the Rh species not only promote the hydrogenation process, but also catalyzes the ammonolysis of the Schiff base intermediate, facilitating the selective synthesis of primary amines. This protocol achieves selective reductive amination at 25 °C and 1 atm, providing an energy-efficient route to a broad spectrum of amines.	Nov 2025
I11-High Resolution Powder Diffraction	Polytypes and planar defects revealed in the purine base xanthine using multi-dimensional electron diffraction Helen W. Leung , Royston C. B. Copley , Giulio I. Lampronti , Sarah J. Day , Lucy K. Saunders , Duncan N. Johnstone , Paul A. Midgley Communications Chemistry 8 DOI: 10.1038/s42004-025-01729-2 Diamond Proposal Number(s): [34800] Open Access Show Abstract ▼ Abstract: Layered crystal structures are commonly found across organic and inorganic material systems. When in-plane atomic arrangement remains (nearly) identical, a stacking variation of these layers may result in twinning, planar disorder, or polytypes, a form of polymorphism derived from altering stacking sequences. In this work, we use multi-dimensional electron diffraction (ED) modalities to explore the microstructure of xanthine, an archetypal purine base with a layered crystal structure. Firstly, we identify and characterise the twin operator relating domains of Form I xanthine. We then solve the structure of a new xanthine polymorph, revealing that it is a polytype of Form I. Finally, interfaces between twin and polytype domains are visualised, whilst streaking in the diffraction patterns reveals the presence of planar disorder. Given these observations in the xanthine system, this work suggests that disorder on the nanoscale may be a commonly occurring phenomenon in layered organic molecular crystals.	Nov 2025
I03-Macromolecular Crystallography I04-Macromolecular Crystallography	Discovery and optimization of a non-nucleoside-based series of inhibitors of 2′-deoxynucleoside 5′-monophosphate glycosidase (DNPH1) Bernard Barlaam , Luz Alonso-Crisostomo , Niall A. Anderson , Argyrides Argyrou , Peter C. Astles , Elaine B. Cadogan , Luca Carlino , Gavin W. Collie , Nichola L. Davies , James Hall , Linda Kitching , Xianxi Li , Filippos Michopoulos , Alexander G. Milbradt , Jenni Nikkilä , Sarah Northall , Mark J. O'Connor , Xiaohiu Pei , Joseph Shaw , Danial Slade , Harriet Southgate , Darren Stead , Christopher J. Stubbs , Benjamin C. Whitehurst , Bin Xing , Yihao Yuan , Jie Zhou Journal Of Medical Chemistry DOI: 10.1021/acs.jmedchem.5c02356 Show Abstract ▼ Abstract: DNPH1 is a nucleotide pool sanitizer that cleaves 5-hydroxymethyl-2-deoxyuridine-5-monophosphate (hmdUMP), preventing incorporation of the correspondent non-natural nucleotide into DNA. Recent findings have demonstrated that loss of DNPH1 could potentiate the sensitivity of PARP inhibitors in homologous recombination repair (HRR)-deficient cancers. We report the optimization of a non-nucleoside-based series of DNPH1 inhibitors. Starting from a weak compound 1 (binding affinity pIC50 4.7), we identified compound 38 as a very potent inhibitor of DNPH1 (pIC50 9.3) using DNPH1 X-ray structure-guided drug design. Compound 38 demonstrated target engagement of DNPH1 in the SUM149PT cell line (pIC50 7.2). Using this tool compound, we then report the in vitro pharmacology of a DNPH1 inhibitor in the BRCA1 mutant SUM149PT cell line.	Nov 2025
I04-Macromolecular Crystallography	Accelerated in silico discovery of SGR-1505: A potent MALT1 allosteric inhibitor for the treatment of mature B-cell malignancies Zhe Nie , Michael Trzoss , Andrew T. Placzek , Lynnie Trzoss , Goran Krilov , Shulu Feng , Morgan Lawrenz , Min Ye , Netonia Marshall , Karen H. Dingley , Robert D. Pelletier , W. George Lai , Jeffrey A. Bell , Haifeng Tang , Paul Devine , Zhijie Liu , Peter Skrdla , Roman Shimanovich , Matt Liu , Renchao Wang , Xiaoming Xu , Robert Abel , Karen Akinsanya , Wu Yin Journal Of Medicinal Chemistry DOI: 10.1021/acs.jmedchem.5c01494 Show Abstract ▼ Abstract: MALT1 is a key component of the CARD11-BCL10-MALT1 (CBM) complex downstream from BTK on the B-cell receptor signaling pathway. It is a key mediator of NF-κB signaling and considered a potential therapeutic target for several subtypes of non-Hodgkin’s B-cell lymphomas. By applying advanced physics-based modeling techniques, including combining free energy calculations with machine learning methods and a chemistry-aware compound enumeration workflow, extensive sets of de novo design ideas were explored to quickly identify a novel hit series. Multiparameter optimization allowed efficient prioritization of molecules with good potency and drug-like properties during lead optimization, which led to the discovery of a highly potent MALT1 inhibitor, SGR-1505, with a well-balanced property profile. It demonstrated strong antitumor activity alone and in combination with BTK inhibitor in multiple in vivo B-cell lymphoma xenograft models and progressed to a phase 1 clinical trial in patients with mature B-cell neoplasms.	Oct 2025

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