Pascal Savy

#STORM's Vice President Medicinal Chemistry, Beth Thomas, is presenting at the Society for Medicines Research's 'Modulating RNA with oligonucleotides or small molecules' conference today!   Beth will be presenting from 13.50 - 14.30 BST on the 'Discovery of STC15, the First Molecule Specifically Targeting an RNA Methyltransferase Enzyme to Enter Clinical Development'.   The one-day conference brings together speakers who will explore successful approaches, future opportunities, and novel approaches being explored in industry and academia to exploit ways to downregulate, upregulate or change splicing in protein synthesis for therapeutic purposes.   #lifesciences #biotech #drugdiscovery #research #STC15 #METTL3 #METTL1 #RNA #modification

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Jufang Wu Ludvigsson from AstraZeneca, Sweden presented on “Separation Method Development of Oligonucleotide on Mixed-Mode Column and by 2D–LC–UV–MS at #ISC2024 in Liverpool. This study explored the application of mixed-mode chromatography as an alternative to the conventional ion-pair reversed-phase liquid chromatography used for oligonucleotide analysis. This mixed-mode technique, which combines charge-based and hydrophobic separations, demonstrated stronger retention and more efficient separations compared to traditional C18 columns, according to Ludvigsson.  Ludvigsson’s emphasized this research demonstrated  that this method eliminated the need for ion-pair reagents, although the use of phosphate buffer created MS detection challenges. To address this, the team implemented a two-dimensional LC–UV–MS setup, where the second dimension employed a MS-compatible mobile phase. This approach significantly increased MS signal intensity, allowing for the characterization of the main peaks and impurities, according to Ludvigsson.

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Today in National Book Week (US). But what is the chemistry of the aroma of old and new books #books #chemistry #aroma #booklover #booknerd #sciencecommunication #scienceandtechnology #science #infographic via Compound Interest | Chemistry infographics

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📢 Register now! https://okt.to/Z392jL This conference will showcase exceptional research from final year PhD students and provides the opportunity to network and share ideas. The subjects covered will be wide ranging within organic chemistry such as synthesis, mechanistic studies, methodology, medicinal chemistry, or analysis and computational. #SCI_PostGrad2024 #SCI_PGsymposium2024

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Cell separation techniques are important across all major fields of modern biology, from stem cell research to drug discovery. This infographic, written by Molly Rose Campbell for Technology Networks, explores the reasons for #cell isolation, the various techniques used and the key downstream applications of such #techniques. https://lnkd.in/eqR3vJyN

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As I used to do microinjection quite often at Scripps, this is an interesting technology to me - delivery of a single molecule into a cell with nano-pipette. Cool! https://lnkd.in/eXEvze4S

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Why are target-specific antibody libraries useful for working with challenging targets? With limited predictive accuracy, AI-designed libraries offer a way to begin tackling 'undruggable' targets, like GPCRs and Ion Channels. #biotech #machinelearning #antibodyengineering

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Simply and fast solvent preparation for peptide synthesis.

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Spin-out Chromatwist has won a prestigious Innovate UK Smart grant to co-fund a £0.5 million project that will take its novel dyes to the next level, enhancing their brightness and staining indices to make cells and cellular structures stand out more clearly during bio-imaging. The funding from Innovate UK, the UK’s innovation agency covers 70% of the project costs. It will also allow ChromaTwist, which is currently raising funds, to push on with technical development and prepare for scale-up and commercial launch, to continue its collaboration with The Babraham Institute in Cambridge, UK. ChromaTwist was founded as a spin-out following the discovery of a new class of fluorescent materials at the University of Birmingham, and is developing over 70 innovative patented UV excitable dyes that emit blue through to red (and potentially into the Near IR). The dyes promise to improve understanding of complex biological processes, leading to more precise diagnostics and new therapies. The company has already developed the dye chemistry to enable conjugation to antibodies and demonstrated exceptional utility and promise in flow cytometry and multiphoton microscopy. Several global flow cytometry players have tested the ChromaTwist conjugates and reproduced the ChromaTwist data. They are now eagerly waiting for the next iteration of ChromaTwist dyes, which have the potential to set new standards in the field. Professor Jon Preece, FRSC, CEO of ChromaTwist, said: “We can take the development of our UV excitable dyes to the next level, and forge a deeper collaboration with the world-renowned flow cytometry facility at the Babraham Institute.” Dr Rachael Walker, Head of Flow Cytometry at the Babraham Institute, added, “I am delighted to continue our productive partnership. Our diverse group of users will be able to test these dyes across a range of biological sample types.” ChromaTwist has already raised funding from existing angel investors, Angel Groups, and private equity investment, and was identified as ‘one to watch’ in the Nature Research 2020 Spinoff Prize.  For commercial information and investment please contact Jon Preece on LinkedIn or via the contact form on the ChromaTwist website: https://lnkd.in/exASY5cT #Innovation #BioImaging #FlowCytometry #ChromaTwist #UVExcitableDyes #ScientificResearch #Diagnostics #InnovateUK #BiomedicalResearch #FluorescentDyes #CellBiology #TherapeuticDevelopment Royal Society of Chemistry | International Society for Advancement of Cytometry | Royal Microscopical Society | Euro-BioImaging

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I am beyond pleased to say that our two Arginase inhibitor papers are now out in J Med Chem ASAPs: https://lnkd.in/e6qUGVSp https://lnkd.in/e-RzNfcq Arg was the first project I worked on at AZ eight years ago - a very unusual introduction to drug discovery! In synthesis, we had no cross-coupling, no chromophores, and wonky behavior by both NMR and Mass Spec. The key step in the first paper is an Ireland-Claisen rearrangement! In medchem we had no passive permeability, minimal liver clearance, and essentially no off-targets. We ultimately used a prodrug strategy...but here I am spoiling all the good stuff :)

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RNA interference using small interfering RNA (siRNA) molecules has emerged as a promising therapeutic modality. To accelerate the discovery of novel siRNAs, WuXi AppTec has established an integrated platform encompassing siRNA sequence design, chemical synthesis/modification, delivery ligand exploration, and activity/off-target assessment. At this year’s TIDES USA conference, our scientists presented a poster showcasing the effectiveness of this platform in conducting a comprehensive study on complement component 5 (C5) siRNAs, identifying chemically modified C5-targeting siRNAs that exhibit potent inhibition of C5 mRNA with minimal off-target effects. Click 👇 to learn more. Questions? Contact us here: https://lnkd.in/eG97YXCs #Biotech #BioPharma #DrugDiscovery #siRNA #ComplementC5 #TIDES #TIDESUSA https://lnkd.in/euHcGvpX

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https://lnkd.in/gaX7bWa5 Happy to publish the article titled "Non-Nucleoside Lycorine-Based Analogs as Potential DENV/ZIKV NS5 Dual Inhibitors" discusses the use of lycorine analogs to target the NS5 RNA-dependent RNA polymerase of dengue and Zika viruses. Through virtual screening, molecular dynamics, and ADMET analysis, the study identified 12 promising lycorine analogs, which showed superior binding affinities compared to ribavirin. These analogs, especially those with distinct enantiomers, present promising avenues for antiviral development against both viruses. Great work with Luke Achenie in Virginia Tech, Paola Andrea Caicedo Burbano in ICESI, Andrés Felipe Vásquez Jiménez, Maria Francisca Villegas-Torres, Yasser Hayek Orduz, Adrian_Camilo Rodríguez_Ararat, Felipe Sierra Hurtado

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A relatively simple peptide modification could unlock a whole class of targets for drug discovery, new research shows. Researchers at the University of Birmingham, in collaboration with the Universities of Bristol and Leeds, successfully demonstrated a route by which peptides could be modified to make them promising reagents for disease diagnostics and drug discovery. Traditional targets in drug discovery are enzymes such as proteases and kinases. These proteins are attractive targets because they have well defined "binding sites" for their substrates—the molecules with which the enzymes interact. It is now relatively straightforward to develop molecules that mimic the substrate and which inhibit or modify the function of the target. In contrast, interactions between proteins—so called protein-protein interaction (PPIs)—regulate most biological functions, including that of enzymes. PPIs are far more numerous than traditional drug discovery targets, so blocking PPIs potentially opens-up a much wider range of drug targets. PPIs have traditionally been considered too difficult to use as drug targets, however, because their binding sites are larger, with fewer grooves or pockets to which small molecule compounds can bind. Understanding how PPIs occur and how to control this represents a first step towards drug discovery against these important targets. In the new study, published in Chemical Science, the team focused on a PPI that involves β-strand formation at the interface. A β-strand is a specific type of secondary structure that is used to build 3D structure in proteins. By taking a small peptide sequence from the part of the protein where the β-strand forms, and making modifications to its backbone, the team were able to show it binds more quickly and more strongly to the target. "Our modification uses relatively simple chemistry and has taught us about how peptides bind to their targets in a β-strand conformation and how to control binding," said lead researcher Professor Andy Wilson, "This in turn opens up the path to drug discovery for β-strand mediated PPIs targets." The team has shown how this could be done for one specific type of PPI—the SIM/SUMO interaction, which in itself plays fundamental roles in protein stability, response to stress and the cell cycle. The next steps will be to demonstrate the approach can be generalized for multiple different PPIs.

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*Molecules of the Month - July Edition* This month, our MotM focuses on Target Protein Degradation and some of the medicinal chemistry approaches that are applied within this area of drug discovery. Read on to find out how LCC's proprietary linkers, virtual libraries and parallel synthesis capabilities can help accelerate you drug discovery efforts. 👇 #TargetProteinDegradation #Linkers #VirtualLibraries #DrugDiscovery

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From the Bollong lab Cysteine reactive groups are a mainstay in the design of covalent drugs and probe molecules, yet only a handful of electrophiles are routinely used to target this amino acid. Here, we report the development of scalable thiol reactivity (STRP), a method which enables the facile interrogation of large chemical libraries for intrinsic reactivity with cysteine. High throughput screening using STRP identified the azetidinyl oxadiazole as a moiety that selectively reacts with cysteine through a ring opening-based mechanism, capable of covalently engaging cysteine residues broadly across the human proteome. We show the utility of this reactive group with the discovery of an azetidinyl oxadiazole containing a small molecule that augments the catalytic activity of the deubiquitinase UCHL1 in vitro and in cells by covalently modifying a cysteine distal to its enzymatic active site. This study adds a novel cysteine targeting group to the electrophilic lexicon and provides robust methodology to rapidly surveil libraries for reactivity with cysteine.

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Transform your postdoc journey  For early-career researchers, securing funding and establishing your own research track record can be daunting.  Building a robust plan for advancing your research career in today’s fast-changing research landscape is possible.  Discover from this video how other ECRs like you have accelerated their research careers by participating in Cruxes Innovation’s Trek Program. What difference could designing your own research career planning playbook make for you? Comment below: we’d love to hear your ideas!  #reserachtoimpact Science & Technology Australia

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We’d like to feature this very popular paper which was published in Antibody Therapeutics. This paper was published just one year ago and already received 7,500+ views/downloads and 5 citations. The corresponding author of this excellent review article is Dr. Ying Li at ProBio. Antibody Therapeutics is the official journal of Chinese Antibody Society, and is an international peer-reviewed, open access journal published by Oxford University Press. Antibody Therapeutics is indexed by ESCI, PubMed and Scopus (2023 CiteScore: 8.7). You are welcome to visit the official website of the journal (see link below) and submit your therapeutic antibody related manuscripts to our journal. https://lnkd.in/gsTu_U2 #antibodies #antibody #antibodytherapeutics #mabs #mab #biologics

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