Lukas Junk retweetet
Degradation strategy prevents survival of tuberculosis bacterium (free w/ registration) bioworld.com/articles/69679…
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Lukas Junk
119 posts
Lukas Junk
@lukasjunk
Synthetic medicinal chemist at HIPS/UdS in Saarbrücken with a focus on peptidic natural products. Also skateboarder and wannabe musician
Saarbrücken, Deutschland Beigetreten Ekim 2009
149 Folgt87 Follower
@Real_Dr_Kessler synthesis was rather straightforward and fun since we just had to dimerize the precursors... but being in the way-beyond-Ro5 space (MW > 2000) is not so fun when trying to optimize PK properties 🥲
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All complaining about the size of PROTACs should look at those molecules: HomoBacPROTACs. Great to see this finally published: Clp-targeting BacPROTACs impair mycobacterial proteostasis and survival cell.com/cell/fulltext/…
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The second half of our homo-BacPROTAC story is now out in @CellCellPress (even before the other half is accepted)! @DHoi93 walks you through the awesome biology behind this study.
Huge thanks to everyone involved @clausen_lab @ChemHaWei @SchmiedelVolker @somrajguha03 & many more
David Hoi@DHoi93
Excited to share our recent work from the @clausen_lab published in @CellPressNews as part 2 of the BacPROTAC story. Here we use targeted protein degradation as an antibiotics strategy to induce self-elimination of essential mycobacterial Clp proteins. sciencedirect.com/science/articl…
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@DHoi93 @Boehringer it was a pleasure working with you folks at IMP, knowing our compounds are in such talented hands :)
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A shoutout to @lukasjunk and our partners at @Boehringer RCV for synthesizing these new chemical modalities. chemrxiv.org/engage/chemrxi…
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Excited to share our recent work from the @clausen_lab published in @CellPressNews as part 2 of the BacPROTAC story. Here we use targeted protein degradation as an antibiotics strategy to induce self-elimination of essential mycobacterial Clp proteins. sciencedirect.com/science/articl…
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@HartungIngo In den Mitteilungseinstellungen (unter iOS ganz unten) auch Testalarms via Cell Broadcast erlaubt?
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Bei mir gar nicht. Zwei Handys, einmal O2, einmal T-Online. Keine SMS, kein Warnton. Wohne mitten in der Stadt. Dafür 3mal Sirenen aus unterschiedlichen Richtungen: 11 Uhr, 11.15 Uhr (Entwarnung?), 12 Uhr (Sirene auf Sommerzeit?). Zu Weihnachten vielleicht ein Fax-Gerät wünschen!
Bundesministerium des Innern@BMI_Bund
Am 8. Dezember 2022 findet der bundesweite #Warntag2022 statt. Am Aktionstag wird zum ersten Mal auch #CellBroadcast erprobt, mit dem Warnungen an viele Mobilfunkgeräte verschickt werden können. Wie das funktioniert? Das @BBK_Bund informiert: bbk.bund.de/DE/Warnung-Vor…
Darmstadt, Germany 🇩🇪 Deutsch
Lukas Junk retweetet
"BacPROTAC" ist unser "Stichwort des Monats"!
— Ein Team um @clausen_lab (@IMPvienna) & Markus Kaiser (@unidue) übertrug das Konzept des PROTAC-intiierten Proteinabbaus auf Bakterien – und macht damit die Entwicklung neuartiger #Antibiotika möglich … 👉 laborjournal.de/rubric/stichwo…
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@agrossfield @leslievosshall @HHMINEWS @ardemp shortdoi.org will turn any doi into a 6-letter one. saw it once in a talk and it just makes sense
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We're doing a thing! Speakers @HHMINEWS Science Meetings will no longer put journal names on their talk slides.
Instead display first author, year, PMID (or DOI) like @ardemp
Why?
-end prestige-signaling
-people can actually find reference
#nojournalnamesontalkslides
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@Carbolution @janboehm gehört aber zum „Weinanbaugebiet Mosel“, früher Mosel-Saar-Ruwer. Der Fehler hat also seine Gründe de.m.wikipedia.org/wiki/Mosel_(We…
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@LSE_editors Thank you so much! The editing and suggestions from @MilkaKostic helped a lot in streamlining the story.
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@rs_mito Probably nothing. The cyclomarins are highly selective for mycobacterial ClpC1, we don't even see any effects on other gram-positive or gram-negative bacteria
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I’m excited to share our work on the development of bacterial PROTACs acting against Mycobacterium tuberculosis :) Our "homo-BacPROTACs" are able to kill drug-resistant Mtb by inducing the degradation of ClpC1, an essential protein in mycobacteria.
doi.org/jgd4
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@christine_m_le thanks Christine :) I thought so since I heard he was a postdoc in the Lautens lab. The chemistry-world is rather small after all
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@lukasjunk Congratulations! By the way, I know Harald very well 😊
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This is the first time that TPD and the BacPROTAC concept have been used to construct antibiotics. It’s a totally new way of killing bacteria. Big thanks go out to everyone involved and the great teams at
@Saar_Uni, @Boehringer, @IMPvienna. @clausen_lab @somrajguha03 @ChemHaWei
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In an SAR study of a library of homo-BacPROTACs, we investigated their solubility, permeability, binding and antibacterial properties. These findings pave the way for further improvements on the way to make BacPROTACs feasible as drugs against TB.
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Upon dimerization, we observed a jump in MIC against Mtb by one order of magnitude! The degradation of the target protein leads to an efficient killing of the bacteria. It even kills multi-drug-resistant Mtb and those residing in macrophages.
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Guiding you through the paper:
We connected two cyclomarin units using click chemistry or olefin metathesis to make BacPROTACs that hijack the unfoldase ClpC1 and cause it to be degraded by its own associated protease ClpP1P2.
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@Titz_Lab höchswahrscheinlich spacex Starlink Satelliten die noch nicht an ihrer finalen Destination sind
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