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Alexander L. Nielsen

@alexanderln.bsky.social
350 followers 92 following 24 posts

senior scientist @ novo nordisk | tweets about (cyclic) peptides | christian heinis & christian a olsen alumni | views are my own ex-twitter: alexanderln91

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Alexander L. Nielsen @alexanderln.bsky.social · 04/06/2026
Happy to share the latest macrocycle paper from the Heinis lab, which I was happy to play a small part in during my postdoc. Big congrats to co-first authors Xinjian and Lluc. Now out in @natchembio.nature.com www.nature.com/articles/s41...
nature.com
Generation of membrane-permeable cyclic peptides inhibiting protein–protein interaction - Nature Chemical Biology
Membrane-permeable cyclic peptides offer access to difficult intracellular targets but discovery remains challenging. Here the authors show that cell-active cyclic peptides can be identified by screen...
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Alexander L. Nielsen @alexanderln.bsky.social · 25/03/2026
We are hiring (again)! Come join our team of curious scientists at our main research hub in Måløv (Copenhagen area). Great opportunity for PhD/postdocs looking at industry. #chemjobs www.novonordisk.com/content/nnco...
novonordisk.com
Scientist/Senior Scientist for Peptide Research
Check out this open position at Novo Nordisk. Starting a career with us is your opportunity to improve the lives of millions of people.
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Alexander L. Nielsen @alexanderln.bsky.social · 24/03/2026
We are hiring! Looking for a Senior Director to support our exciting innovation efforts in peptide research (Copenhagen area, DK) #chemjobs www.novonordisk.com/content/nnco...
novonordisk.com
Sr. Director for Peptide Innovation
Check out this open position at Novo Nordisk. Starting a career with us is your opportunity to improve the lives of millions of people.
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Alexander L. Nielsen @alexanderln.bsky.social · 10/06/2025
Looking for a PhD in peptide chemistry? Apply for this exciting collaboration between Novo Nordisk and the Grob lab at ETH!
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Alexander L. Nielsen @alexanderln.bsky.social · 02/06/2025
Thank you for the kind words, Joshua!
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Alexander L. Nielsen @alexanderln.bsky.social · 02/06/2025
To finish off. Thanks to all collaborators on this work! I had the most amazing postdoc surrounded by talented co-workers and collaborators. It would not have been possible without you. (10/🧵-end) Also, I hope you enjoy the work and can apply the model and/or the CAPA amino acids in future work.
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Alexander L. Nielsen @alexanderln.bsky.social · 02/06/2025
Hopefully the model can/will be re-fitted with additional permeability data from even larger/complex libraries in the future. However, this was how it ended with me leaving academia (albeit staying in research, now in industry at Novo🐂👨‍🔬). (9/🧵)
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Alexander L. Nielsen @alexanderln.bsky.social · 02/06/2025
Finally, we teamed up with @pschwllr.bsky.social @rebeccaneeser.bsky.social who prepared a random forest model that can readily applied to estimate the membrane permeability of designed cyclic peptides. Model available on GitHub: github.com/schwallergro... (8/🧵)
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Alexander L. Nielsen @alexanderln.bsky.social · 02/06/2025
This gave us deep insight into the permeability of an unprecedented number of compounds in CAPA. We also recapitulated that exceeding a MW of 800 Da, a PSA of 250 Å2, or 5 HBDs had a small chance of having a good membrane permeability - although there can be outliers. (7/🧵)
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Alexander L. Nielsen @alexanderln.bsky.social · 02/06/2025
After some synthesis iterations, we designed a diverse random library of 192 CA-peptides. Despite some issues with diketopiperazine (DKP) by-products, we obtained 143 macrocycles for subsequent crude analysis in CAPA. (6/🧵)
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Alexander L. Nielsen @alexanderln.bsky.social · 02/06/2025
We next developed a crude synthesize strategy to synthesize crude CA-tagged macrocycles (based on previous workflow: onlinelibrary.wiley.com/doi/10.1002/...), and we saw that crude peptides tested in CAPA gave rise to similar half-maximal cell penetration (CP50) values to purified compounds. (5/🧵)
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Alexander L. Nielsen @alexanderln.bsky.social · 02/06/2025
To make CAPA directly compatible with automated SPPS, I synthesized new (and less polar) CA-tagged amino acids that allowed for easy and direct incorporation into macrocycles. We showed that permeability was nicely retained in known model peptides such as CsA bearing the new amino acid(s). (4/🧵)
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Alexander L. Nielsen @alexanderln.bsky.social · 02/06/2025
One of the caveats with CAPA for passively permeable compounds is the relatively large (commercial) succinyl-chloroalkane tag (Suc-CA). Permeability was negatively impacted >10-fold compared to installing a smaller CA-tag onto macrocycle scaffolds with known good passive permeability. (3/🧵)
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Alexander L. Nielsen @alexanderln.bsky.social · 02/06/2025
This work was conceptualized by me and my good friend and co-first author Dr. Christian Bech-Bartling at @ucph.bsky.social. We merged our shared interests for macrocycles, high-throughput and the chloroalkane penetration assay (CAPA, first developed by @chemkritzer.bsky.social) and got started (2/🧵)
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Alexander L. Nielsen @alexanderln.bsky.social · 02/06/2025
Very pleased to share the 'last' first-author paper from my postdoc with Prof. Christian Heinis at EPFL. Now out in its final form in @angewandtechemie.bsky.social as a 'Very Important Paper' 🔥 (1/🧵) #chemsky onlinelibrary.wiley.com/doi/10.1002/...
onlinelibrary.wiley.com
Bulk Measurement of Membrane Permeability for Random Cyclic Peptides in Living Cells to Guide Drug Development
Some cyclic peptides can cross membranes, which is highly attractive for drug development, but it remains difficult to accurately predict membrane permeability or to test it experimentally for large ...
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Alexander L. Nielsen @alexanderln.bsky.social · 08/05/2025
Exciting opportunity to join our US research site! #chemjobs careers.novonordisk.com/job/Lexingto...
careers.novonordisk.com
Senior Scientist I - Peptide and Macrocycle Chemistry
Senior Scientist I - Peptide and Macrocycle Chemistry
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Alexander L. Nielsen @alexanderln.bsky.social · 24/03/2025
Sharing for better reach: Join a fun, talented and social lab. #postdocjob available in the Knowles group (Univ. of Cambridge). Experience with mRNA/phage/yeast display is a plus. www.jobs.cam.ac.uk/job/50546/
jobs.cam.ac.uk
Post-Doctoral Research Associate (Fixed Term) - Job Opportunities - University of Cambridge
Post-Doctoral Research Associate (Fixed Term) in the Yusuf Hamied Department of Chemistry at the University of Cambridge.
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Alexander L. Nielsen @alexanderln.bsky.social · 19/02/2025
Thanks for the (long) ride! 😎
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Reposted by Alexander L. Nielsen
Carlos Moreno-Yruela @carlosmyruela.bsky.social · 19/02/2025
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
pubs.acs.org
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 ...
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Alexander L. Nielsen @alexanderln.bsky.social · 16/02/2025
Our work on macrocyclic HDAC11 inhibitors is now out in JACS Au! pubs.acs.org/doi/10.1021/... #openaccess #chemsky
pubs.acs.org
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 ...
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Reposted by Alexander L. Nielsen
Carlos Moreno-Yruela @carlosmyruela.bsky.social · 04/02/2025
#SIRT7 is a histone deacetylase with highly specific activity on #chromatin substrates. We just published mechanism-based #cryoEM structures of #SIRT7 on nucleosomes to understand its activity 👇 www.nature.com/articles/s41... (1/8) #ChemBio #ChemSky
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Alexander L. Nielsen @alexanderln.bsky.social · 13/01/2025
Come join Craig in his new lab in wonderful Copenhagen! 🇩🇰
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Reposted by Alexander L. Nielsen
Karl Gademann @karlgademann.bsky.social · 09/01/2025
We are hiring! Exciting project on the performance enhancement of peptides. Check out and share: jobs.uzh.ch/job-vacancie...
jobs.uzh.ch
UZH: PhD Student Position in Peptide Chemistry
A PhD Student position is available in the group of Prof. Dr. Karl Gademann, located in the Department of Chemistry at the University of Zurich (Switzerland). Our group combines the synthesis of natur...
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Reposted by Alexander L. Nielsen
Daniela Danková @danieladankova.bsky.social · 13/12/2024
Happy to share the latest preprint from my PhD studies on the discovery of de novo macrocyclic inhibitors of HDAC11. This was a great collaboration between @christianaolsen.bsky.social lab (@carlosmyruela.bsky.social, @tnhansen.bsky.social) and Christian Heinis lab (@alexanderln.bsky.social).
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Reposted by Alexander L. Nielsen
Christian A. Olsen @christianaolsen.bsky.social · 10/12/2024
New preprint @chemrxiv.bsky.social on discovery of macrocyclic inhibitors of HDAC11 with the Christian Heinis #EPFL Main contributors @danieladankova.bsky.social, @alexanderln.bsky.social, @carlosmyruela.bsky.social 🙏 @ERC_Research, @novonordiskfond, @DFF_raad for 💶 chemrxiv.org/engage/chemr...
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Alexander L. Nielsen @alexanderln.bsky.social · 09/12/2024
Happy to share a fun collaboration between EPFL and UCPH initiated by @carlosmyruela.bsky.social, Christian Heinis, @christianaolsen.bsky.social and I! Big shout-out to @danieladankova.bsky.social who spearheaded the project. Now out on @chemrxiv.bsky.social chemrxiv.org/engage/chemr...
chemrxiv.org
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 ...
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Alexander L. Nielsen @alexanderln.bsky.social · 30/11/2024
Amazing work by my colleagues! Now out in Nature Comms! www.nature.com/articles/s41...
nature.com
Photochemically-enabled, post-translational production of C-terminal amides - Nature Communications
C-terminal α-amidated peptides are attractive therapeutic targets, but preparative methods to access amidated pharmaceuticals are limited both on lab and manufacturing-scale. Here, the authors report ...
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Alexander L. Nielsen @alexanderln.bsky.social · 15/01/2024
Latest paper from the Heinis lab. Solid-phase peptide synthesis in 4 × 384 well-plates to prepare 1,536 peptides per run! Out now in J. Pept. Sci! onlinelibrary.wiley.com/doi/10.1002/...
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Alexander L. Nielsen @alexanderln.bsky.social · 28/12/2023
The latest paper from the Heinis on the development of orally available cyclic peptides is finally out in Nature Chemical Biology! Big congrats to Manuel who spearheaded this project! www.nature.com/articles/s41...
nature.com
De novo development of small cyclic peptides that are orally bioavailable - Nature Chemical Biology
Cyclic peptides show promise for modulating difficult disease targets; however, they often cannot be administered orally. The authors developed a method to synthesize and screen large libraries of sma...
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