Center of Medical Biotechnology

Welcome to @unidue.bsky.social!
We’re happy to have you on board and wish you a fantastic start!

Many thanks to @lanabuzuk.bsky.social from the @hellerschmiedlab.bsky.social for taking over this account over the past few days and sharing updates from the #17GPS @unidue.bsky.social. Really appreciate you keeping everyone in the loop!

🎉 Congratulations to all of our poster prize winners!

#17GPS

Alkyne Derivatives of SARS-CoV-2 Main Protease Inhibitors Including Nirmatrelvir Inhibit by Reacting Covalently with the Nucleophilic Cysteine Nirmatrelvir (PF-07321332) is a nitrile-bearing small-molecule inhibitor that, in combination with ritonavir, is used to treat infections by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2...

Have a look at the alkyne derivatives of SARS-CoV-2 main protease inhibitors here: doi.org/10.1021/acs....

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Check out his work on mass spectrometric assays that monitor the deubiquitinase activity of SARS-CoV-2 papin-like protease here: doi.org/10.1016/j.bm...

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Last talk of the session was given by Lennart Brewitz from the Polish Academy of Sciences. He presented activity assays with substrate-derived oligopeptides enable development of substrate selective inhibitors of the SARS-CoV-2 papain-like protease.

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Next, Robert Zitterbart from Gyros Protein Technologies. He spoke about reliable high throughput chemo selective catch and release purification of peptides from TFA cleavage cocktails without precipitation

#17GPS

Structure‐Based Design of Bicyclic Helical Peptides That Target the Oncogene β‐Catenin A bicyclic peptide is reported that combines two hydrocarbon staples with i,i+4 and i,i+3 spacing, respectively. In the resulting i,i+4,i+7 crosslink topology, a central spiro center connects two mac...

Next up, Juan Lizandra Pérez from @vuamsterdam.bsky.social and the group of @tomngrossmann.bsky.social spoke about the design and characterisation of beta-caternin site-specific cell-permeable beta-hairpin-based inhibitors. Take a look at the work here: doi.org/10.1002/anie...

#17GPS

Take a look at how they disentangled direct and indirect effects on dephosphorylation using chemical modulators of PP1 in cellular contexts here: doi.org/10.1039/D3SC...

3/3

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FEBS Press Synthetic trap-peptides facilitate the identification of complete holoenzymes that bind to the target sequence remarkably close to the phosphorylation site. PP4 bound to, but did not dephosphorylate,....

Check out their recent work on synthetic trap-peptides in identifying a TOM complex phosphatase: doi.org/10.1111/febs...

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Kicking off the last session of the symposium, our keynote speaker @mkoehn.bsky.social from
@unibonn.bsky.social spoke about peptide tools used to dissect phosphatase-substrate interactions. Have a look at the human dephosphorylation database (DEPOD) via the link www.depod.org

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Last talk of the session was given by Raimund Maier from Iris Biotech GmbH, who spoke about Tag-Assisted Peptide Synthesis (TAPS) enabling more efficient and sustainable peptide synthesis and purification

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Improvement of Analysis and Transferability in Peptide Purification: From HPLC to FPLC and Back Again A predictive workflow enables accurate transfer from analytical HPLC to preparative FPLC for peptide purification. Systematic evaluation of key chromatographic parameters identified particle size, fl...

As well as the recent publication on the improvement of analysis and transferability in peptide purification here: doi.org/10.1002/psc....

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Revealing deamidation and isoaspartate formation during peptide analysis, purification and storage by tandem mass spectrometry Interest in peptides and peptidomimetics continues to grow, particularly in the context of drug discovery and development. However, spontaneous chemical modifications such as deamidation and isoaspart...

Check out their most recent publication on deamidation and isoaspartate formation during peptide analysis, purification and storage by tandem mass spectrometry: pubs.rsc.org/en/content/a...

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Next, Christian Steuer from @ethz.ch presented the analytical challenges and opportunities in peptide drug discovery, with lessons learned from chromatography and mass spectrometry.

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Synthesis of Fusahexin and Characterization of a Natural β-Turn Dipeptide We describe the first synthesis of the natural cyclic hexapeptide Fusahexin cyclo(-ala-Leu-ehr=Pro-leu-Leu) (1) containing the bicyclic dipeptide ehr=Pro, a tetrahydro-1,3-oxazin-4-one formed from erythronine and proline. Fusahexin and several other peptides were obtained either by using the bicyclic dipeptide Fmoc-ehr=Pro-OH (2) in SPPS or by late-stage oxidation of a precursor peptide aldehyde. In all cases studied, the bicyclic dipeptide ehr=Pro cyclizes by acid-promoted condensation, forming the bridge head of the fused bicyclic ring exclusively in R configuration. The conformational behavior of Fusahexin and several stereochemical variants was characterized by NMR and modeling. Its convenient accessibility and its transferability make the β-turn dipeptide ehr=Pro a useful general reverse-turn dipeptide.

Interested in the synthesis of Fusahexin? Check out the following study: doi.org/10.1021/acs....

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#17GPS

Synthesis of β,β‐Dinaphthyl Amino Acids: Towards Molecular Gearing in Peptides and Mini‐Proteins Amino acids bearing two aromatic side chains are studied here for their ability to align in rotor-like assemblies in a synthetic protein. Based on quantitative analysis of 1H NMR reference nuclei, we...

Want to know more about the synthesis of beta-beta-dinaphthyl amino acids? Check out the published work here: doi.org/10.1002/chem...

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Next up, Armin Geyer from the Philips Universität Marburg spoke on the synthesis of natural and designed Cbeta-functionalised peptides.

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Iodine-Mediated Tryptathionine Formation Facilitates the Synthesis of Amanitins Synthetic methods on the macrocyclization of peptides are of high interest since they facilitate the synthesis of various types of potentially bioactive compounds, e.g. addressing targets like protein–protein-interactions. Herein, we report on an efficient method to construct tryptathionine-cross-links in peptides between the amino acids Trp and Cys. This reaction not only is the basis for the total synthesis of the death cap toxin α-amanitin but also provides rapid access to various new amanitin analogues. This study for the first time presents a systematic compilation of structure–activity relations (SAR) of amatoxins with regard to RNA polymerase II inhibition and cytotoxicity with one amanitin derivative of superior RNAP II inhibition. The present approach paves the way for the synthesis of structurally diverse amatoxins as future payloads for antibody–toxin conjugates in cancer therapy.

Interested in how Amanitins were synthesised in the lab? Check out the study here:
doi.org/10.1021/jacs...

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Paenilamicins are context-specific translocation inhibitors of protein synthesis - Nature Chemical Biology The paenilamicins are hybrid nonribosomal peptide–polyketide compounds that inhibit protein synthesis. Here the authors reveal that paenilamicins bind to a unique site on the ribosome, where they inte...

Want to know more about paenilamicins? Check out the following publication:
doi.org/10.1038/s415...

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#17GPS

Fighting Antimicrobial Resistance: Innovative Drugs in Antibacterial Research This article provides an overview over antibacterial drugs investigated in the past three decades. Aspects of the compound's origins, their cellular targets, the antibacterial spectrum and proof-of-c...

Kicking off the next session, our keynote speaker Roderich Süssmuth from TU Berlin spoke about peptide antibiotics that matter, linking structure to biological effect. You can nicely find the information on fighting antimicrobial resistance in their review: doi.org/10.1002/anie...

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Elucidating Leader Peptide–Enzyme Dynamics in Lactazole Biosynthesis Using mRNA Display Thiopeptides are a class of ribosomally synthesized and post-translationally modified peptides (RiPPs) that show promise for drug discovery. Their biosynthesis depends on leader peptide recognition, whereby multiple enzymes are recruited to process a core region into the mature natural product. Here, we identify sequence determinants of the leader peptide–enzyme dynamics in a thiopeptide biosynthesis. Using the flexible in vitro (FIT)-Laz translation platform, we examined how leader mutations influence modifications performed by the enzymes that together complete lactazole biosynthesis. Initial DNA template translations informed single amino acid saturation mutagenesis using mRNA display. This revealed leader mutations that modulate enzyme recognition, as validated by aligning enrichment scores with observed modification. This study provides important insights into the underexplored role of RiPP leader peptides and informs the design of improved pseudonatural product libraries.

Check out his most recent work in the Suga Lab here: doi.org/10.1021/jacs...

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Assembling branched and macrocyclic peptides on proteins A two-step, biocompatible strategy enables site-specific generation of branched and macrocyclic peptide–protein conjugates. Solvent-exposed cysteines on proteins are modified by a small bifunctional r...

He presented work from his time as a PhD student in the group of Christoph Nitsche at the Australian National University. Check out his work on assembling branched and macrocyclic peptides on proteins here: pubs.rsc.org/en/content/a...

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Last talk of the session was from Sven Ullrich from the Suga Lab in @utokyoofficial.bsky.social. His talk focussed on biocompatible chemistry for constrained peptides and compact proteins

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Next, Christian Behn from CEM GmbH presented on massive waste reduction for solid phase peptide synthesis, and on greening reversed-phase liquid chromatography methods through replacement of acetonitrile with ethanol.

#17GPS

Peptide Boronic Acids by Late‐Stage Hydroboration on the Solid Phase Transition metal-catalyzed hydroboration of peptide alkenes and alkynes with readily available reactants selectively yields aliphatic- and vinylboronic acids in a straightforward, on-resin, late-stag...

Check out the work on peptide boronic acids by late-stage hydroboration on the sold phase here: doi.org/10.1002/advs...

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Late‐Stage Amination of Peptides on the Solid Phase The introduction of amines into peptides via an on-resin iodination-substitution reaction sequence provides access to a wide variety of modifications, including amine-based metal ligands. Primary, se...

Next up, Franziska Thomas from @uniheidelberg.bsky.social presented from the Chemist’s Toolbox, showing new synthetic approaches for therapeutic peptides and beyond. Interested in how to do late-stage amination of peptides on the solid phase? Have a read here: doi.org/10.1002/chem...

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Total Synthesis and Structure Correction of the Cyclic Lipodepsipeptide Orfamide A For the total synthesis of orfamide A an efficient synthesis format for cyclic lipodepsipeptide natural products on solid phase was developed. A strategy using side chain anchoring, an ester building....

Check out the work on the total synthesis and structure correction of the cyclic lipodesipeptide Orfamide A here: doi.org/10.1002/chem...

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Semiautomated Total Synthesis of the Cyclic Lipodepsipeptide Anikasin The total synthesis of Pseudomonas-derived cyclic lipodepsipeptide anikasin was achieved. Using a depsipeptide building block and balanced protecting groups on the branching d-allo-Thr residue, the synthesis was established semiautomatically on a synthesizer. Buffered deprotections minimized side reactions and afforded synthetic anikasin and its enantiomer. Biological activity studies indicated that anikasin’s mode of action is directly resulting from its physicochemical properties.

Have a look at the semiautomated total synthesis of the cyclic lipodesipeptide Anikasin here: doi.org/10.1021/acs....

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SiR‐XActin: A Fluorescent Probe for Imaging Actin Dynamics in Live Cells SiR-XActin is a far-red fluorescent probe for live-cell imaging of actin that avoids genetic modification and minimizes disruption of actin dynamics, due to its lower binding affinity. Based on jaspl...

Day 3 of the #Peptide Symposium began with a talk from our keynote speaker Hans-Dieter Arndt from @uni-jena.de. The talk focussed on the synthesis and investigations of (and with) cyclodesipeptides. Want to know more about SiR-XActin? doi.org/10.1002/anie...

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