Activity-based protein profiling (ABPP) as a proteomic tool allows measuring the
activity of enzyme classes or distinct proteins in their cellular context,
annotating the function of uncharacterized proteins, and investigating the
target profile of small molecule inhibitors. In our latest review, published in
the Israel Journal of Chemistry, we provide an update to our previous review,
focussing on the recent advances of ABPP of oxidases and also reductases. This
article will be part of a special issue dedicated to Prof. Benjamin F. Cravatt,
the pioneer of ABPP and recipient of the 2022 Wolf Prize in Chemistry.
Today Christian Lembacher-Fadum defended his PhD thesis on "Synthesis of
N-Heterocyclic Inhibitors and Tool Compounds for Drug Discovery and Chemical
Biology". We want to congratulate Christian on this fantastic achievement, as he
has also been working in industry since december 2021 while writing his thesis,
and thank him very much for all the years as a great colleague to all of us at
Today, our group alumni Dr. Thomas Schlatzer received his promotio sub
auspiciis Praesidentis rei publicae, which is the highest possible distinction
for academic achievements for a doctoral degree in Austria. In this solemn
event, Thomas was awarded with his doctoral degree and a ring of honour by
president Dr. Alexander van der Bellen.
Thomas is currently working as a postdoctoral researcher in the group of Prof.
Veronique Gouverneur at the University of Oxford and we wish him all the best
for his future career!
In this study, published in Bioorganic & Medicinal Chemistry, we describe the
design and synthesis of the so far most effective peptide-based inhibtor of
dipeptidyl peptidase III (DPP3). Starting from the slowly converted peptide
substrate tynorphin and by replacing the scissile bond with a fluoroethylene
bioisostere, thenewly reported ground state inhibitor outcompetes the previously
reported transition state mimetic inhibitor HER.
In our latest collaboration with the Institute of Molecular Biosciences at the
University of Graz, published in Journal of the American Chemical Society, we
reportthe development and biological characterization of the first
small-molecule inhibitor of human Adipose Triglyceride Lipase (ATGL), which is a
key enzyme in lipolysis. Detailed insights into the enzyme–inhibitor
interactions could be revealed through combined analysis of mouse- and
human-selective inhibitors, chimeric ATGL proteins, and homology models.
In this series of three back-to-back papers, we report about a complete library of building blocks featuring the side chains of all amino acids relevant for protein-protein interactions (PPIs). Via sequential Pd cross-coupling, these building blocks can be connected to form teraryl-based alpha-helix mimetics as inhibitors of PPIs. The papers are referred to as Parts 3-5 as they follow up on our two previous publications in this field.
Parts 3 and 4 describe core fragments with two leaving groups of differentiated reactivity (iodide and triflate or iodide and bromide, respectively). Part 5 describes a complementary set of pyridine boronic acid building blocks.
In our newest publication, we describe the first total synthesis of ETM-204, which is a metabolite of the chemotherapeutic agent Trabectidin (Yondelis®). Key step of the synthesis is a modified Pomeranz–Fritsch cyclization to assemble the isoquinoline ring. The paper was published in Monatshefte für Chemie.
In this study, published in Chemistry – A European Journal, we disclose the design, synthesis and biophysical characterization of peptidomimetic inhibitors of dipeptidyl peptidase III (DPP3). The inhibition of this metalloprotease is based on the entropy-driven release of water from the closing binding cleft as confirmed by ITC measurement and X-ray crystallography.
Hydrophilic phosphorus ligands are crucial for transition metal-catalyzed reactions in water or biphasic solvents. In our latest review, published in Advanced Synthesis & Catalysis, we summarize the progress in the synthesis of novel water-soluble phosphines over the past decade. Additionally, we describe recent applications of transition metal catalysis in aqueous solvents based on hydrophilic P-donor ligands.
This minireview summarizes state of the art approaches for the activity-based protein profiling (ABPP) of oxidoreductases and discusses the scope and limitations of established methodologies.
In our latest publication in Bioorganic & Medicinal Chemistry, we disclose structure–activity relationship (SAR) studies of small molecule inhibitors of murine adipose triglyceride lipase (mATGL) that resulted in the development of Atglistatin as powerful tool compound.
In this contribution published in Tetrahedron, we report a synthetic protocol for the stereoselective preparation of highly functionalized aminohydroxythiols. The methodology is based on a SmI2/LiBr-mediated reductive coupling of Ellman N-sulfinylimines with aldehydes.
In this study a highly modular synthesis of quateraryl alpha-helix mimetics as inhibitors for protein-protein interactions (PPIs) is presented. The combination of an electroorganic as well as a Pd-catalyzed cross-coupling provides efficient access to quaterarylic systems. This work was published in Catalysts.
Anna Migglautsch just defended her PhD thesis on “Development of inhibitors of human adipose triglyceride lipase (hATGL)”. We want to thank her for the last years in which she became an essential member of the Institute and congratulate on doing an amazing job at her defense!
The Austrian Research Promotion Agency (FFG) just published a press release on the development of a drug candidate for diabetes treatment. This joint research project between the Institute of Molecular Biosciences (University of Graz) and the Institute of Organic Chemistry (TU Graz) focuses on the synthesis of small molecule inhibitors of the adipolytic enzyme ATGL.
In our latest publication we disclose a palladium-catalyzed protocol for the highly chemo- as well as regioselective S-allylation of thiols. This transformation developed at the Institute of Organic Chemistry offers several advantages over established reaction for the synthesis of thioethers. The paper was published in Advanced Synthesis & Catalysis and highlighted as “very important publication”!
TU Graz just published a press release on the development of a new method for the site-selective lipidation of proteins. This palladium-mediated reaction was developed at the Institute of Organic Chemistry (TU Graz) in collaboration with the Institute of Biological Chemistry (University of Vienna) and recently published in the Journal of American Chemical Society.