Admission requirements
Core course in MSc Chemistry - Chemical Biology and MSc Life Science and Technology, elective course in MSc Chemistry - Energy & Sustainability,
For students with a BSc in MST, LST or equivalent. Of note, through the selected topics an overview of the current status of chemical biology research that is based on organic chemistry is given. The course builds on the B.Sc. (MST) course ‘biomolecular chemistry’ and a fundamental understanding on organic chemistry transformations is required. The course is intended to be complementary to the courses on Molecular Cell Biology, Medicinal Chemistry and Chemical Immunology as well as the organic chemistry courses taught in the MSc Chemistry program at Leiden University.
Description
Chemical biology is a relatively young and rapidly growing interdisciplinary of research. In chemical biology, phenomena, or problems, that are intrinsically rooted in biology are studied using strategies, tools and techniques developed through chemical research. This description is of course broad and one can also argue that there is nothing new to chemical biology, with the fields of bioorganic chemistry, biochemistry and molecular biology already established for decades. Chemical biology is however more than hype, or rebranding of old fields, for several reasons. First, whereas molecular scientists are capable of designing and creating molecules of increasing size and complexity, structural and analytical biology is now capable of studying biomolecules at an increasingly detailed molecular level, and do so in the context of increasingly complex biomolecule mixtures, up to cellular and organismal levels. Second and perhaps because of this, chemical biology develops as a truly interdisciplinary research area, with chemists striving to move into biology and biologists aiming to employ chemistry in their research.
Chemical biology is very much in development, and many chemical biology studies are methodology-driven, proof-of-concept studies. The youth of chemical biology as a scientific discipline is also reflected in university education programs, with most chemical biology courses and programs internationally recently established. This is true also for the chemical biology program at Leiden University, which has started recently (2014-2015). Aim of this course is to provide an overview – based on original research papers – of the development of chemical biology research in the two decades, dating back to the early days of chemical biology research. Main focus is on organic chemistry in relation to biological research: the design and application of organic molecules for biological research, and making use of the organic chemistry properties of biomolecules in their study and manipulation. It should be noted that there are many chemistry disciplines (analytical chemistry, inorganic chemistry, structural chemistry to name a few) that contribute to chemical biology and thus the examples discussed here are by no means all encompassing. Organic chemistry, or the design of bioactive organic molecules, is one of the focus areas of the Leiden chemical biology research.
In this course, several original research papers on a specific topic will be discussed in 15 lectures on campus if allowed by corona rules. The course will cover the following topics in chemical biology: bio-orthogonal chemistry, activity-based protein profiling, protein targeted degradation, chemical proteomics, cleavable linkers, conditional fluorescence, photochemistry, click to release strategies, protein ligation methodologies and genetic code expansion.
All lectures will be on campus and will be recorded if all participants agree. Lectures 14 and 15 will be devoted to group discussions on “open topics in chemical biology”, in which teams of two to three students select a chemical biology paper and present the scope and results to the class (potential papers of interest are also provided on Brightspace, and students are also encouraged to delve in the literature and pick a paper of their own liking).
Students are asked to read the discussion papers prior to lectures 1-15. The lectures themselves are intended for interactive discussions on these papers, rather than a classical address. Focus in the discussions is intended to be on the general strategies and the organic chemistry design behind the research, rather than on extensive discussion on the experimental details. For the first few topics, introductory videos will be uploaded to have an overview prior to discussing the papers. PowerPoint presentations summarizing the main idea and results of the research papers for all other topics will be uploaded in Brightspace. These summaries will be discussed following the student presentations, if time allows.
The discussion papers are a mix of original studies defining a new chemical biology area of research combined with recent examples. All discussion papers are available on Brightspace alongside some relevant literature – mostly reviews – for further reading on the subject at hand. Though the course is built around individual topics, the underlying research papers often combine elements in more integrative approaches.
Course Objectives
At the end of the course, students should be able to:
Read, analyze and ultimately judge research articles on chemical biology.
Interrelate and integrate various areas of chemical biology research.
Make an independent analysis of scientific problems.
Learn and describe modern chemical biology techniques and their applications.
Analyze relevant specialist literature.
Present and explain a research article on chemical biology and formulate questions to the rest of the students.
Identify the limitations of particular chemical biology techniques/applications, and think on potential solutions for such limitations.
Formulate verifiable hypotheses and come up with ideas and/or solutions to research questions in chemical biology.
Ultimately, present a critical thinking on chemical biology research.
Timetable
Schedule information can be found on the website of the programmes.
You will find the timetables for all courses and degree programmes of Leiden University in the tool MyTimetable (login). Any teaching activities that you have sucessfully registered for in MyStudyMap will automatically be displayed in MyTimeTable. Any timetables that you add manually, will be saved and automatically displayed the next time you sign in.
MyTimetable allows you to integrate your timetable with your calendar apps such as Outlook, Google Calendar, Apple Calendar and other calendar apps on your smartphone. Any timetable changes will be automatically synced with your calendar. If you wish, you can also receive an email notification of the change. You can turn notifications on in ‘Settings’ (after login).
For more information, watch the video or go the the 'help-page' in MyTimetable. Please note: Joint Degree students Leiden/Delft have to merge their two different timetables into one. This video explains how to do this.
Mode of instruction
The course consists of 15 lectures on campus.
Assessment method
The final grade will be obtained by the sum of a written exam (90%) and a student presentation (10%).
Students will give presentations of the papers selected for each lecture and it is expected that each student will present at least once. Presentations will be evaluated following the rubric used to determine the grade in colloquiums at Leiden University. If there are changes to the assessment method, these will be announced via Brightspace a minimum of 10 working days before the originally scheduled exam date.
In the final written exam, one or two new research articles will be provided and the exam will consist of a written examination with around 10 essay questions varying in difficulty. The students will have to read and analyze the research articles, and answer the questions by integrating various areas of chemical biology research that have been discussed during the course. The students will have to describe chemical biology techniques and their applications, identify the limitations of particular chemical biology techniques/applications, and think on potential solutions for such limitations. The re-take exam will have a similar format.
Reading list
All reading materials, discussion papers and further reading materials, will be published on Brightspace.
Lecture 1: Bioorthogonal Chemistry 1: Click Chemistry
Discussion papers
1) E. Saxon and C. R. Bertozzi, Cell surface engineering by a modified Staudinger reaction, Science 2000, 287, 2007.
http://science.sciencemag.org/content/287/5460/2007
One of the first research papers in the field and the one defining bioorthogonal chemistry.
2) N. J. Agard, J. M. Baskin, J. A. Prescher, A. Lo and C. R. Bertozzi, A comparative study on bioorthogonal reactions with azides, ACS Chem Biol 2006, 1, 644. https://pubs.acs.org/doi/abs/10.1021/cb6003228
This study compares azide-alkyne click reactions and Staudinger ligation – two of the main bioorthogonal reactions applied today – on their merits.
3) N. Devaraj, R. Upadhyay, J. B. Haun, S. A. Hilderbrand and R. Weissleder, Fast and sensitive pretargeted labeling of cancer cells through a tetrazine/trans-cyclooctene cycloaddition, Angew. Chem. Int. Ed. 2009, 48, 7013.
https://onlinelibrary.wiley.com/doi/abs/10.1002/anie.200903233
This paper presents what is now termed the ‘Inverse electron-demand Diels-Alder’ ligation: one of the most versatile and applied bioorthogonal reactions of today.
Lecture 2: Bioorthogonal Chemistry 2: Examples
Discussion papers
1) Y. Kho, S. C. Kim, C. Jiang, D. Barma, S. W. Kwon, J. Cheng, J. Jaunbergs, C. Weinbaum, F. Tamanoi, J. Falck and Y. Zhao, A tagging-via-substrate technology for detection of farnesylated proteins, Proc. Natl. Acad. Sci. USA 2004, 101, 12579.
https://www.pnas.org/content/101/34/12479.short
Bioorthogonal tagging of farnesylated proteins.
2) R. J. B. Schäfer, M. R. Monaco, M. Li, A. Tirla, P. Rivera-Fuentes, and H. Wennemers, The bioorthogonal isonitrile−chlorooxime ligation. J. Am. Chem. Soc. 2019, 141, 18644−18648
https://pubs.acs.org/doi/pdf/10.1021/jacs.9b07632.
This study describes a new bio-orthogonal reaction between isonitriles and chlorooximes and its orthogonality to the strain-promoted azide−alkyne cycloaddition in live-cells. It also describes the development of bioorthogonal antibodies for in situ studies.
3) Nature-inspired bioorthogonal reaction: development of β‐caryophyllene as a chemical reporter in tetrazine ligation. Bioconjug. Chem. 2018, 29, 2287−2295.
https://pubs.acs.org/doi/pdf/10.1021/acs.bioconjchem.8b00283
Bioorthogonal IEDDA reaction using β-caryophyllene and tetrazine applied to both in vitro and live cell imaging.
Lecture 3: Activity-Based Protein Profiling 1
Discussion papers
1) Y. Liu, M. P. Patricelli and B. F. Cravatt, Activity-based protein profiling: the serine hydrolases, Proc. Natl. Acad. Sci. USA 1999, 96, 14694.
https://www.pnas.org/content/96/26/14694.short
The first paper on activity-based protein profiling and the paper defining the field.
2) D. Greenbaum, K. Medzihradszky, A. Burlingame and M. Bogyo, Epoxide electrophiles as activity-dependent cysteine protease profiling and discovery tools, Chem Biol 2000, 7, 569.
https://www.sciencedirect.com/science/article/pii/S1074552100000144
Broadening the ABPP scope to cysteine proteases.
3) W. Rut, K. Groborz, L. Zhang, X. Sun, M. Zmudzinski, B. Pawlik, X. Wang, D. Jochmans, J. Neyts, W. Młynarski, R. Hilgenfeld and M. Drag, SARS-CoV-2 Mpro inhibitors and activity-based probes for patient-sample imaging, Nat. Chem. Biol. 2021, 17, 222-228
https://www.nature.com/articles/s41589-020-00689-z.pdf
SARS-CoV-2 Mpro activity-based probes provide a structural platform for the development of new antiviral agents and diagnostic tools for SARS-CoV-2 infections.
Lecture 4: Activity-based protein profiling 2
Discussion papers
1) G. de Bruin, B. T. Xin, M. Kraus, M. van der Stelt, G. A. van der Marel, A. F. Kisselev, C. Driessen, B. I. Florea and H. S. Overkleeft, A set of activity-based probes to visualize human (immuno)proteasome activities, Angew. Chem. Int. Ed. 2016, 55, 4199.
https://onlinelibrary.wiley.com/doi/abs/10.1002/anie.201509092
Activity-based probes to study threonine hydrolases: proteasomes.
2) L. I. Willems, N. Li, B. I. Florea, M. Ruben, G. A. van der Marel, H. S. Overkleeft, Triple bioorthogonal ligation strategy for simultaneous labeling of multiple enzymatic activities, Angew. Chem. Int. Ed. 2012, 51, 4431.
https://onlinelibrary.wiley.com/doi/full/10.1002/anie.201200923
A paper on three bioorthogonal reactions in concert in ABPP.
3) Z. Armstrong, C.-L. Kuo, D. Lahav, B. Liu, R. Johnson, T. J. M. Beenakker, C. de Boer, C.-S. Wong, E. R. van Rijssel, M. F. Debets, B. I. Florea, C. Hissink, R. G. Boot, P. P. Geurink, H. Ovaa, M. van der Stelt, G. M. van der Marel, J. D. C. Codeé,J. M. F. G. Aerts, L. Wu, H. S. Overkleeft and G. J. Davies, Manno-epi-cyclophellitols enable activity-based protein profiling of human α‐mannosidases and discovery of new Golgi mannosidase II inhibitors, J. Am. Chem. Soc. 2020, 142, 13021−13029.
https://pubs.acs.org/doi/abs/10.1021/jacs.0c03880
A paper on activity-based retaining alpha mannosidases profiling, merging ABPP with a contemporary high-throughput assay format for screening of inhibitors: fluorescence polarization.
Lecture 5: Protein targeted degradation
Discussion papers
1) K. M. Sakamoto, K. B. Kim, A. Kumagai, F. Mercurio, C. M. Crews, and R. J. Deshaies, Protacs: chimeric molecules that target proteins to the Skp1–Cullin–F box complex for ubiquitination and degradation, Proc. Natl. Acad. Sci. USA 2001, 98, 8554.
https://www.pnas.org/content/pnas/98/15/8554.full.pdf
First paper describing proteolysis targeted chimeras (PROTACs).
2) S. M. Banik, K. Pedram, S. Wisnovsky, G. Ahn, N. M. Riley and C. R. Bertozzi, Lysosome-targeting chimaeras for degradation of extracellular proteins, Nature 2020, 584, 291.
https://www.nature.com/articles/s41586-020-2545-9.pdf
Development of LYTACs: a new targeted protein degradation strategy for directing proteins for lysosomal degradation capitalizing on the cation-independent mannose-6-phosphate receptor (CI-M6PR).
3) P.-H. Chen, Z. Hu, E. An, I. Okeke, S. Zheng, X. Luo, A. Gong, S. Jaime-Figueroa and C. M. Crews Modulation of phosphoprotein activity by phosphorylation targeting chimeras (PhosTACs), ACS Chem. Biol. 2021, 16, 2808.
https://pubs.acs.org/doi/pdf/10.1021/acschembio.1c00693
This paper describes the first phosphorylation targeting chimeras PhosTACs. Although this paper is not related to PROTACs per se, these PhosTAC chimeras also induce ternary complexes, recruiting a Ser/Thr phosphatase to a protein to mediate its dephosphorylation. Contrary to PROTACs, PhosTACs aim to provide target gain-of-function opportunities to manipulate protein activity and open new ways for targeted posttranslational modifications (PTMs).
Lecture 6: Chemical proteomics
Discussion papers
1) P. Gygi, B. Rist, S. A. Gerber, F. Turecek, M. H. Gelb and R. Aebersold, Quantitative analysis of complex protein mixtures using isotope-coded affinity tags, Nat. Biotech. 1999, 17, 994.
https://www.nature.com/articles/nbt1099_994
Groundbreaking paper on the use of designer chemicals to quantify peptide/protein levels.
2) E. Weerapana, C. Wang, G. M. Simon, F. Richter, S. Khare, M. B. D. Dillon, D. A. Bachovchin, K. Mowen, D. Baker and B. F. Cravatt, Quantitative reactivity profiling predicts functional cysteines in proteomes, Nature 2010, 468, 790.
https://www.nature.com/articles/nature09472
Paper introducing stoichiometry as a readout for reactive thiols in chemical proteomics.
3) K. M. Backus, B. E. Correia, K. M. Lum, S. Forli, B. D. Horning, G. E. González-Páez, S. Chatterjee, B. R. Lanning, J. R. Teijaro, A. J. Olson, D. W. Wolan and B. F. Cravatt, Proteome-wide covalent ligand discovery in native biological systems, Nature 2016, 534, 570.
https://www.nature.com/articles/nature18002.pdf
Quantitative analysis of cysteine- reactive small-molecule fragments screened in human proteomes and cells. Covalent ligands for >700 cysteines are identified in both druggable proteins and proteins deficient in chemical probes, including transcription factors, adaptor/scaffolding proteins, and uncharacterized proteins.
Lecture 7: Cleavable linkers
Discussion papers
1) S. H. L. Verhelst, M. Fonovic and M. Bogyo, A mild chemically cleavable linker system for functional proteomics applications, Angew. Chem. Int. Ed. 2007, 46, 1284.
https://onlinelibrary.wiley.com/doi/full/10.1002/anie.200603811
An early example of a designer linker stable in physiological conditions yet cleavable under mild conditions.
2) P. P. Geurink, B. I. Florea, N. Li, M. D. Witte, J. Verasdonck, C.-L. Kuo, G. A. van der Marel and H. S. Overkleeft, A cleavable linker based on the levulinoyl ester for activity-based protein profiling, Angew. Chem. Int. Ed. 2010, 49, 6802.
https://onlinelibrary.wiley.com/doi/full/10.1002/anie.201001767
Example on the adaptation of a known protective group in synthetic organic chemistry to a bioorthogonal cleavable linker.
3) D. K. Miyamoto, H.A. Flaxman, H.-Y. Wu, J. Gao and C. M. Woo, Discovery of a celecoxib binding site on prostaglandin E synthase (PTGES) with a cleavable chelation-assisted biotin probe, ACS Chem. Biol. 2019, 14, 2527.
https://pubs.acs.org/doi/abs/10.1021/acschembio.9b00511
A diphenylsilane cleavable linker in a chelation-assisted biotin affinity-based probe assists the identification of a novel binding site for celecoxib on prostaglandine E synthase.
Lecture 8: Chemical Biology of Kinase inhibitors
Discussion papers
1) B. R. Lanning, L. R. Whitby, M. M. Dix, J. Douhan, A. M. Gilbert, E. C. Hett, T. O. Johnson, C. Joslyn, J. C. Kath, S. Niessen, L. R. Roberts, M. E. Schnute, C. Wang, J. J. Hulce, B. Wei, L. O. Whitely, M. M. Hayward and B. F. Cravatt, A road map to evaluate the proteome-wide selectivity of covalent kinase inhibitors, Nat. Chem. Biol. 2014, 10, 760.
https://www.nature.com/articles/nchembio.1582
Chemical proteomics study on identification of kinases that can be covalently inhibited.
2) Q. Zhao, X. Ouyang, X. Wan, K. S. Gajiwala, J. C. Kath, L. H. Jones, A. L. Burlingame and J. Taunton, Broad-spectrum kinase profiling in live cells with lysine-targeted sulfonyl fluoride probes, J. Am. Chem. Soc. 2017, 139, 680.
https://pubs.acs.org/doi/abs/10.1021/jacs.6b08536
Kinase-active site lysines are recruited for covalent, irreversible modification.
3) B. Adhikari, J. Bozilovic, M. Diebold, J. Denise Schwarz, J. Hofstetter, M. Schröder, M. Wanior, A. Narain, M. Vogt, N. Dudvarski Stankovic, A. Baluapuri, L. Schönemann, L. Eing, P. Bhandare, B. Kuster, A. Schlosser, S. Heinzlmeir, C. Sotriffer, S. Knapp and E. Wolf, PROTAC-mediated degradation reveals a non-catalytic function of AURORA-A kinase. Nat. Chem. Biol. 2020, 16, 1179.
https://www.nature.com/articles/s41589-020-00652-y.pdf
The authors develop a PROTAC for AURORA-A kinase which induces a cooperative ternary complex between AURORA-A and CEREBLON and ultimately promotes apoptosis in cancer cell lines.
Lecture 9: Conditional fluorescence
Discussion papers
1) Z. Gao, O. G. Ovchinnikova, B.-S. Huang, F. Liu, D. E. Williams, R. J. Andersen, T. L. Lowary, C. Whitfield, and S. G. Withers, High-throughput “FP-Tag” assay for the identification of glycosyltransferase Inhibitors, J. Am. Chem. Soc. 2019, 141, 2201.
https://pubs.acs.org/doi/pdf/10.1021/jacs.8b109402)
The development of a high-throughput screening based on a fluorescence polarization quenched substrate that gets cleaved and activated by KpsC glycosyltransferase.
2) A. K. Yadav, D. L. Shen, X. Shan, X. He, A. R. Kermode and D. J. Vocadlo, Fluorescence quenched substrates for life cell imaging of human glucocerebrosidase activity, J. Am. Chem. Soc. 2015, 137, 1181.
https://pubs.acs.org/doi/10.1021/ja5106738
In this paper fluorescence quenched probe design is expanded to glycosidases.
3) Y. Urano, D. Asanuma, Y. Hama, Y. Koyama, T. Barrett, M. Kayima, T. Nagano, T. Watanabe, A. Hasegawa, P. L. Choyke and H. Kobayashi, Selective molecular imaging of viable cancer cells with pH-activatable fluorescence probes, Nat. Med. 2009, 15, 104.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2790281/
Study on the use of protonation as a means to activate fluorescence in cell imaging.
4) G. de Bruin, B.-T. Xin, B. I. Florea and H. S. Overkleeft, Proteasome subunit selective activity-based probes report on proteasome core particle composition in a native polyacrylamide gel electrophoresis fluorescence-resonance energy transfer assay, J. Am. Chem. Soc. 2016, 138, 9874.
https://pubs.acs.org/doi/10.1021/jacs.6b04207
FRET ABPP to assess the nature of protein assemblies.
Lecture 10: Photochemistry and biology
Discussion papers
1) C. G. Parker, A. Galmozzi, Y. Wang, B. E. Correia, K. Sasaki, C. M. Joslyn, A. S. Kim, C. L. Cavallaro, R. M. Lawrence, S. R. Johnson, I. Narvaiza, E. Saez and B. F. Cravatt, Ligand and target discovery by fragment-based screening in human cells, Cell 2017, 168, 527.
https://doi.org/10.1016/j.cell.2016.12.029
A paper making use of photoaffinity-based fragments to screen in human cells for their molecular targets facilitating the discovery of bioactive molecules.
2) M. N. Gandy, A. W. Debowsky and K. A. Stubbs, A general method for affinity-based proteomic profiling of exo-alpha-glucosidases, Chem. Commun. 2011, 47, 5037
https://pubs.rsc.org/en/content/articlelanding/2011/CC/c1cc10308c
A paper describing photoaffinity labeling for the class of glycosidases not forming covalent intermediates with their substrates: inverting glycosidases.
3) M. Toebes, M. Coccoris, A. Bins, B. Rodenko, R. Gomez, N. J. Nieuwkoop, W. van de Kasteele, G. F. Rimmelzwaan, J. B. A. G. Haanen, H. Ovaa and T. N. M. Schumacher, Design and use of conditional MHC I class I ligands, Nat. Med. 2006, 12, 246.
https://www.nature.com/articles/nm1360
Photocleavable peptide epitopes for ligand exchange.
4) W. A. Velema, J. P. van der Berg, M. J. Hansen, W. Szymanski, A. J. M. Driessen and B. L. Feringa, Optical control of antibacterial activity, Nat. Chem. 2013, 5, 924.
https://www.nature.com/articles/nchem.1750
Paper on optical switching of an inactive compound to an active antibiotic and an early example of photopharmacology.
Lecture 11: Click-to-release
Discussion papers
1) J. B. Pawlak, G. P. P. Gential, T. Ruckwardt, J. S. Bremmers, N. J. Meeuwenoord, F. A. Ossendorp, H. S. Overkleeft, D. V. Filippov and S. I. van Kasteren, Bioorthogonal deprotection on the dendritic cell surface for chemical control of antigen cross-presentation, Angew. Chem. Int. Ed. 2015, 54, 5628.
https://onlinelibrary.wiley.com/doi/full/10.1002/ange.201500301#support-information-section
Use of the ‘classical’ Staudinger reduction in chemical biology research.
2) M. Wilkovitsch, M. Haider, B. Sohr, B. Herrmann, J. Klubnick, R. Weissleder, J. C. T. Carlson, and H. Mikula, A cleavable C2‑symmetric trans-cyclooctene enables fast and complete bioorthogonal disassembly of molecular probes, J. Am. Chem. Soc. 2020, 142, 19132.
https://pubs.acs.org/doi/pdf/10.1021/jacs.0c07922
This paper describes an extracellular and intracellular bioorthogonal disassembly strategy using omnidirectional tetrazine-triggered cleavage.
3) E. Maurits, M. J. van de Graaff, S. Maiorana, D. P. A. Wander, P. M. Dekker, S. Y. van der Zanden, B. I. Florea, J. J. C. Neefjes, H. S. Overkleeft and S. I. van Kasteren. Immunoproteasome inhibitor−doxorubicin conjugates target multiple myeloma cells and release doxorubicin upon low-dose photon irradiation, J. Am. Chem. Soc. 2020, 142, 7250.
https://pubs.acs.org/doi/pdf/10.1021/jacs.9b11969
This paper describes a doxorubicin conjugate that is released in the active site by UV photocleavage using a photolabile 2-(4-nitrophenyl)benzofuran chromophore.
Lecture 12: Protein Ligation Strategies
Discussion papers
1) M. W. Popp, J. M. Antos, G. M. Grotenbreg, E. Spooner and H. L. Ploegh, Sortagging: a versatile method for protein labeling, Nat. Chem. Biol. 2007, 3, 707.
https://www.nature.com/articles/nchembio.2007.31
Implementation of a natural protein ligase enzyme for chemical tagging of proteins.
2) G. Gaietta, T. J. Deerinck, S. R. Adams, K. Bouwer, O. Tour, D. W. Laird, G. E. Sosinsky, R. Y. Tsien and M. H. Ellisman, Multicolor and electron microscopic imaging of connexin trafficking, Science 2002, 296, 503.
https://science.sciencemag.org/content/296/5567/503
A study that combines tagging of fusion proteins, pulse-chase labeling and chemical metal deposition for electron microscopy.
3) L. Kambanis, T. S. Chisholm, S. S. Kulkarni and R. J. Payne, Rapid one-pot iterative diselenide–selenoester ligation using a novel coumarin-based photolabile protecting group, Chem. Sci., 2021, 12, 10014.
https://pubs.rsc.org/en/content/articlepdf/2021/sc/d1sc02781f
The development of an iterative one-pot peptide ligation strategy that capitalises on the diselenide–selenoester ligation reaction.
Lecture 13: Genetic Code Expansion
Discussion papers
1) L. Wang, A. Brock, B. Herberich and P. G. Schultz, Expanding the genetic code of Escherichia coli, Science 2001, 292, 498.
https://science.sciencemag.org/content/292/5516/498
Groundbreaking paper on the introduction of a non-proteinogenic amino acid.
2) T. A. Mollner, P. G. Isenegger, B. Josephson, C. Buchanan, L. Lercher, D. Oehlrich, D. Flemming Hansen, S. Mohammed, A. J. Baldwin, V. Gouverneur and B. G. Davis. Post-translational insertion of boron in proteins to probe and modulate function, Nat. Chem. Biol. 2021, 17, 245.
https://www.nature.com/articles/s41589-021-00883-7.pdf
Very recent paper describing a mild, direct, site-selective way of introducing of boronoalanine (Bal) in proteins.
3) M. Fottner, A.-D. Brunner, V. Bittl, D. Horn-Ghetko, A. Jussupow, V. R. I. Kaila, A. Bremm and K. Lang, Site-specific ubiquitylation and SUMOylation using genetic-code expansion and sortase, Nat. Chem. Biol. 2019, 15, 276.
https://doi.org/10.1038/s41589-019-0227-4
This recent paper describes site-specific attachment of Ubls to nonrefoldable, multidomain proteins and enables inducible and ubiquitin-ligase-independent ubiquitylation of proteins in mammalian cells with temporal control.
Lectures 14 and 15: Free topics
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Prof.dr. Hermen Overkleeft, Dr. Marta Artola Perez de Azanza
Remarks
Lecture, Subject and Literature
1 Bioorthogonal Chemistry 1: Click Chemistry
2 Bioorthogonal Chemistry 2: Examples
3 Activity-Based Protein Profiling 1: Serine and Cysteine Hydrolases
4 Activity-based protein profiling 2: Proteasomes and Glycosidases
5 Protein targeted degradation
6 Chemical proteomics
7 Cleavable linkers
8 Chemical Biology of Kinase inhibitors
9 Conditional fluorescence
10 Photochemistry and biology
11 Click-to-release
12 Protein Ligation Strategies
13 Genetic Code Expansion
14 Group Presentations on papers selected by yourself
15 Group Presentations on papers selected by yourself
According to OER article 4.8, students are entitled to view their marked examination for a period of 30 days following the publication of the results of a written examination. Students should contact the lecturer to make an appointment for such an inspection session.