Maric Lab

Excited to share the new Peptide Libraries volume via Springer Nature (Methods in Molecular Biology series):
link.springer.com/book/10.1007...

19 protocols & perspectives from leading labs on #PeptideLibraries design, synthesis & #screening.

Thanks to co-editor Ronald Frank and all contributors!

Congrats! Beautiful spotlight on the cover of #JACS!

Our eSylites are on the cover of the current #JACS issue! Check it out 👇

jacs-covers-25

On the cover of this week's #JACS: "eSylites: Synthetic Probes for Visualization and Topographic Mapping of Single Excitatory Synapses"

Read it here 🔗 buff.ly/tunBPI2
#ChemSky

We are looking for a PhD candidate in medicinal / organic chemistry with a passion for drug discovery to join our young and enthusiastic team @univie.ac.at. For details, visit: jobs.univie.ac.at/job/Universi.... Reposts are very much appreciated!

Elucidation of short linear motif-based interactions of the MIT and rhodanese domains of the ubiquitin-specific protease 8 - Biology Direct Ubiquitin-specific protease 8 (USP8) is a deubiquitinating enzyme with essential functions in protein trafficking and stability. It is a multidomain protein, with an N-terminal MIT (microtubule intera...

We uncover that the #USP8 rhodanese domain is a #peptide binding module that binds short linear motifs in potential substrates: biologydirect.biomedcentral.com/articles/10....

Chimeric deubiquitinase engineering reveals structural basis for specific inhibition of the mitophagy regulator USP30 - Nature Structural & Molecular Biology Kazi et al. report the crystal structure of the mitochondrial deubiquitinase USP, a clinical stage Parkinson’s disease drug target, in complex with a specific inhibitor. The authors delineate a framew...

Super happy to share that our work on the specific inhibition of USP30 - a clinical stage Parkinson's drug target - is now online at NSMB www.nature.com/articles/s41... Have a read if you fancy chimeric protein engineering or a framework for DUB ligandability. Huge congratulations to Nafizul & team!

Happy to share the positive review for "Epitope Sequence and Modification Fingerprints of Anti-Aβ Antibodies" doi.org/10.7554/eLif...
Now online in @elife.bsky.social
Looking forward to sharing the revised version!🔜
@hmariclab.bsky.social @uni-wuerzburg.de @maxplanck.de @unimedizin-goe.bsky.social

Just reviewed @elife.bsky.social
Epitope Sequence and Modification Fingerprints of Anti-Aβ Antibodies

Resource & deep dive into how therapeutic & research #Antibody detect key #AmyloidBeta variants in #AlzheimersDisease

Thanks @unimedizin-goe.bsky.social, @mpi-nat.bsky.social & @uni-wuerzburg.de !

High‐Throughput Tiling of Essential mRNAs Increases Potency of Antisense Antibiotics The systematic tiling of essential genes’ mRNA here presented, proposes a valuable tool for the identification of novel PNA sequences with antibiotic potential. The high-throughput synthetic set up o...

First post, first paper 🤭
Proud to share with all of you our work on mRNA blocking using our own high-throughput antisense approach! doi.org/10.1002/advs...

Many thanks to @hmariclab.bsky.social, @jorg-vogel-lab.bsky.social and especially Linda for the amazing collaboration 😸

And this only the beginning! I’m glad we did that collaboration with the Maric lab. ASOs for the people!

Thrilled to see our work on targeted #mRNA blockade using high-throughput #antisense screening, now published in Advanced Science! 🚀

A true team effort in close collaboration with the @jorg-vogel-lab.bsky.social with special credit to Popella & Danti!

ASOs for the people!
bsky.app/profile/gior...

Our latest paper on the sodium leak channel NALCN complex is now online. We found that the neuronal SNARE proteins syntaxin 1A and SNAP25 inhibit sodium leak currents both in heterologous systems and in neurons!

www.science.org/doi/10.1126/...

Functionalized Docetaxel Probes for Refined Visualization of Mitotic Spindles by Expansion Microscopy Visualizing the ultrastructure of mitotic spindles, the macromolecular machines that segregate chromosomes during mitosis, by fluorescence imaging remains challenging. Here we introduce an azido- and ...

🆕 Our new functionalized docetaxel probe enables superior visualization of dense mitotic spindle structures during cell division by expansion microscopy!

▶️ pubs.acs.org/doi/10.1021/...

Make sure not to miss our latest paper out now in #JACS - presenting eSylites - small, peptide-based probes for precise mapping of neurons, etc.!

Microscale thermophoresis (MST) played a huge part in optimizing the probes structure and sequence for binding affinity.

#ChemicalBiology #Synapse

Super happy to see our work on eSylites finally out in #JACS introducing small peptidic probes for simplified excitatory #Synapse visualization with unprecedented resolution!

Huge thanks to all authors making this possible!

eSylites: Synthetic Probes for Visualization and Topographic Mapping of Single Excitatory Synapses The spatiotemporal organization of the postsynaptic density (PSD) is a fundamental determinant of synaptic transmission, information processing, and storage in the brain. The major bottleneck that prevents the direct and precise representation of the nanometer-scaled organization of excitatory glutamatergic synapses is the size of antibodies, nanobodies, and the genetically encoded fluorescent tags. Here, we introduce small, high affinity synthetic probes for simplified, high contrast visualization of excitatory synapses without the limitations of larger biomolecules. In vitro binding quantification together with microscopy-based evaluation identified eSylites, a series of fluorescent bivalent peptides comprising a dye, linker, and sequence composition that show remarkable cellular target selectivity. Applied on primary neurons or brain slices at nanomolar concentrations, eSylites specifically report PSD-95, the key orchestrator of glutamate receptor nanodomains juxtaposed to the presynaptic glutamate release sites that mediate fast synaptic transmission. The eSylite design minimizes a spatial dye offset and thereby enables visualization of PSD-95 with improved localization precision and further time-resolved discrimination. In particular, we find that individual dendritic spines can contain separate nanodomains enriched for either PSD-95 or its closest homologues, PSD-93 or SAP102. Collectively, these data establish eSylites as a broadly applicable tool for simplified excitatory synapse visualization, as well as a high-end microscopy compatible probe for resolving the PSD organization with unprecedented resolution.

🚀 Excited to share our latest work in #JACS on eSylites!

—Synthetic, high-affinity #ChemicalBiology probes for #SuperResolution #Synapse visualization & precise mapping in neurons and brain slices—without the need for antibodies, tags, or transfection!

📢 Read more: pubs.acs.org/doi/10.1021/...

Our work on macrocyclic HDAC11 inhibitors is now out in JACS Au! pubs.acs.org/doi/10.1021/...
#openaccess #chemsky

Discovery of De Novo Macrocycle Inhibitors of Histone Deacetylase 11 Histone deacetylase (HDAC) enzymes are epigenetic regulators that affect diverse protein function by removing acyl groups from lysine side chains throughout the proteome. The most recently discovered ...

Very happy to see this story out in #JACS_Au!

Discovery of De Novo Macrocycle Inhibitors of Histone Deacetylase 11
pubs.acs.org/doi/10.1021/...

#ChemBio #chemsky #HDAC

We mapped the epitope and PTMs preferences of anti-Aβ, such as Aducanumab, Lecanemab & Donanemab biosimilars.

Big thanks to all authors who made this possible, especially our colleagues at @maxplanck.de and @unimedizin-goe.bsky.social And of course the @hmariclab.bsky.social @uni-wuerzburg.de

👋

Great panel organized by Angela Getz @WCBR with Matt Kennedy, Johannes Hell and ourselves on new tools to understand synapse organization and function 🧪

🚨 Excited to share our work @elife.bsky.social doi.org/10.7554/eLife.98827.2 on targeting Hepatitis B virus #HBV 🦠 capsid aggregation by designed molecules! #DrugDiscovery #ChemBio

Thanks V Khayenko C Makbul @clemensschulte.bsky.social & @boettchercryoem.bsky.social for stunning #CryoEM visuals!

Our joined effort with the the Maric Lab @hmariclab.bsky.social @uniwuerzburg.bsky.social on how to aggregate capsids of Hepatitis B virus inside cells is now out in Elife doi.org/10.7554/eLif... . #cryoEM 🧪❄️🔬

I am super happy to share our latest article entitled "Decoding the molecular interplay of CD20 and therapeutic antibodies with fast volumetric nanoscopy", now published in Science www.science.org/doi/10.1126/...
It was my postdoctoral work mit @sauer-lab.bsky.social Congrats to all the co-authors!

🔬 Ever wondered how therapeutic antibodies work?
3D LLS-TDI-DNA-PAINT and live-cell LLS microscopy allow decoding of the molecular interplay of endogenous CD20 on B cells with therapeutic antibodies.

📄 Read more: www.science.org/doi/10.1126/...

Mode of action of the new microscopy method LLS-TDI-DNA-PAINT. On the top right, the RTX antibody was visualised on a Raij-B cell: it is easy to see how it links the CD20 molecules in the membrane. Bottom right: the hedgehog-shaped appearance of a living Raji B cell after the antibody has bound. The surface protein CD45, which is homogeneously distributed on the cell surface, is also labelled in green. (Image: Arindam Ghosh / University of Würzburg)

Delighted to launch our activities on Bluesky with this great news: Our researchers @sauer-lab.bsky.social show in @science.org, how therapeutic #antibodies interact with B cells – thanks to an innovative method of super-resolution microscopy. Congratulations!
➡️ www.uni-wuerzburg.de/en/news-and-...