Herman S Overkleeft

Publications of Herman S Overkleeft

• Triple Bioorthogonal Ligation Strategy for Simultaneous Labeling of Multiple Enzymatic Activities.

  Authors: Lianne I Willems, Nan Li, Bogdan I Florea, Mark Ruben, Gijsbert A van der Marel, Herman S Overkleeft

  Angewandte Chemie (International ed. in English). 03/2012;

  Three at the same time: A ligation strategy combining tetrazine-norbornene cycloaddition, Staudinger-Bertozzi ligation, and copper(I)-catalyzed click reaction was used to label the three catalyticThree at the same time: A ligation strategy combining tetrazine-norbornene cycloaddition, Staudinger-Bertozzi ligation, and copper(I)-catalyzed click reaction was used to label the three catalytic activities of the proteasome simultaneously in a single experiment. The orthogonality of the three ligation reactions enables selective monitoring of multiple targets at the same time in complex biological samples.

• Automated Solid-Phase Synthesis of β-Mannuronic Acid Alginates.

  Authors: Marthe T C Walvoort, Hans van den Elst, Obadiah J Plante, Lenz Kröck, Peter H Seeberger, Herman S Overkleeft, Gijsbert A van der Marel, Jeroen D C Codée

  Angewandte Chemie (International ed. in English). 02/2012;

  A big step towards routine: The title synthesis provides of mannuronic acid alginate fragments featuring up to 12 cis-mannosidic linkages, in multi-milligram quantities (see scheme; Bn=benzyl,A big step towards routine: The title synthesis provides of mannuronic acid alginate fragments featuring up to 12 cis-mannosidic linkages, in multi-milligram quantities (see scheme; Bn=benzyl, Lev=levulinoyl). Mannuronic acid building blocks were used in a second-generation carbohydrate synthesizer to secure the stereoselective introduction of the β-mannosidic bonds in a fully automated fashion.

• Activity-based protein profiling: an enabling technology in chemical biology research.

  Authors: Nan Li, Herman S Overkleeft, Bogdan I Florea

  Current opinion in chemical biology. 02/2012;

  Activity-based protein profiling (ABPP) is one of the main driving forces in chemical biology and one of the most visible areas where organic chemistry contributes to chemical biology research. InActivity-based protein profiling (ABPP) is one of the main driving forces in chemical biology and one of the most visible areas where organic chemistry contributes to chemical biology research. In recent years, ABPP research has gradually made the transfer from the relatively easy target enzymes (for instance serine hydrolases, cysteine and threonine proteases) toward targeting enzymes that are intrinsically more difficult to address. These include less abundant enzymes, enzymes that do not employ a nucleophilic amino acid residue in their active site and enzymes more particular with respect to their substrate. At the same time, ABPP has started to make a tangible impact on clinical research.

• Fluorous linker facilitated synthesis of teichoic acid fragments.

  Authors: Wouter F J Hogendorf, Lucien N Lameijer, Thomas J M Beenakker, Herman S Overkleeft, Dmitri V Filippov, Jeroen D C Codée, Gijsbert A Van der Marel

  Organic letters. 02/2012; 14(3):848-51.

  The use of perfluorooctylpropylsulfonylethanol as a new phosphate protecting group and fluorous linker is evaluated in the stepwise solution phase synthesis of a number of biologically relevantThe use of perfluorooctylpropylsulfonylethanol as a new phosphate protecting group and fluorous linker is evaluated in the stepwise solution phase synthesis of a number of biologically relevant (carbohydrate substituted) glycerol teichoic acid fragments. Teichoic acid fragments, up to the dodecamer level, were assembled by means of phosphoramidite chemistry, using a relatively small excess of the building blocks and a repetitive efficient purification procedure of the protected intermediates by fluorous solid phase extraction (F-SPE).

• Proteasome inhibitors: an expanding army attacking a unique target.

  Authors: Alexei F Kisselev, Wouter A van der Linden, Herman S Overkleeft

  Chemistry & biology. 01/2012; 19(1):99-115.

  Proteasomes are large, multisubunit proteolytic complexes presenting multiple targets for therapeutic intervention. The 26S proteasome consists of a 20S proteolytic core and one or two 19S regulatoryProteasomes are large, multisubunit proteolytic complexes presenting multiple targets for therapeutic intervention. The 26S proteasome consists of a 20S proteolytic core and one or two 19S regulatory particles. The 20S core contains three types of active sites. Many structurally diverse inhibitors of these active sites, both natural product and synthetic, have been discovered in the last two decades. One, bortezomib, is used clinically for treatment of multiple myeloma, mantle cell lymphoma, and acute allograft rejection. Five more recently developed proteasome inhibitors are in trials for treatment of myeloma and other cancers. Proteasome inhibitors also have activity in animal models of autoimmune and inflammatory diseases, reperfusion injury, promote bone and hair growth, and can potentially be used as anti-infectives. In addition, inhibitors of ATPases and deubiquitinases of 19S regulatory particles have been discovered in the last decade.

• Photoaffinity labeling in activity-based protein profiling.

  Authors: Paul P Geurink, Laurette M Prely, Gijs A van der Marel, Rainer Bischoff, Herman S Overkleeft

  Topics in current chemistry. 01/2012; 324:85-113.

  Activity-based protein profiling has come to the fore in recent years as a powerful strategy for studying enzyme activities in their natural surroundings. Substrate analogs that bind covalently andActivity-based protein profiling has come to the fore in recent years as a powerful strategy for studying enzyme activities in their natural surroundings. Substrate analogs that bind covalently and irreversibly to an enzyme active site and that are equipped with an identification or affinity tag can be used to unearth new enzyme activities, to establish whether and at what subcellular location the enzymes are active, and to study the inhibitory effects of small compounds. A specific class of activity-based protein probes includes those that employ a photo-activatable group to create the covalent bond. Such probes are targeted to those enzymes that do not employ a catalytic nucleophile that is part of the polypeptide backbone. An overview of the various photo-activatable groups that are available to chemical biology researchers is presented, with a focus on their (photo)chemistry and their application in various research fields. A number of comparative studies are described in which the efficiency of various photo-activatable groups are compared.

• Exploring and exploiting the reactivity of glucuronic acid donors.

  Authors: Ana-Rae de Jong, Bas Hagen, Vincent van der Ark, Herman S Overkleeft, Jeroen D C Codée, Gijsbert A Van der Marel

  The Journal of organic chemistry. 11/2011; 77(1):108-25.

  The relative reactivity of glucuronic acid esters was established in a series of competition experiments, in which two thioglucoside and/or thioglucuronic acid ester donors competed for a limitedThe relative reactivity of glucuronic acid esters was established in a series of competition experiments, in which two thioglucoside and/or thioglucuronic acid ester donors competed for a limited amount of activator (NIS-TfOH). Although glucuronic acid esters are often considered to be of very low reactivity, the series of competition reactions revealed that the reactivity of the glucuronic acid esters studied is sufficient to provide productive glycosylation reactions. The latter is illustrated in the synthesis of two Streptococcus pneumoniae trisaccharides, in which the applicability of the two similarly protected frame-shifted thiodisaccharide donors, Glc-GlcA and GlcA-Glc, were compared. The Glc-GlcA disaccharide, featuring the glucuronic acid donor moiety, proved to be the most productive in the assembly of a protected S. pneumoniae trisaccharide.

• Discovery of a potent and highly β1 specific proteasome inhibitor from a focused library of urea-containing peptide vinyl sulfones and peptide epoxyketones.

  Authors: Wouter A van der Linden, Lianne I Willems, Tamer B Shabaneh, Nan Li, Mark Ruben, Bogdan I Florea, Gijs A van der Marel, Markus Kaiser, Alexei F Kisselev, Herman S Overkleeft

  Organic & biomolecular chemistry. 11/2011; 10(1):181-94.

  Syringolins, a class of natural products, potently and selectively inhibit the proteasome and show promising antitumour activity. To gain insight in the mode of action of syringolins, the ureidoSyringolins, a class of natural products, potently and selectively inhibit the proteasome and show promising antitumour activity. To gain insight in the mode of action of syringolins, the ureido structural element present in syringolins is incorporated in oligopeptide vinyl sulfones and peptide epoxyketones yielding a focused library of potent new proteasome inhibitors. The distance of the ureido linkage with respect to the electrophilic trap strongly influences subunit selectivity within the proteasome. Compounds 13 and 15 are β5 selective and their potency exceeds that of syringolin A. In contrast, 5 may well be the most potent β1 selective compound active in living cells reported to date.

• Synthesis of pH-activatable red fluorescent BODIPY dyes with distinct functionalities.

  Authors: Sascha Hoogendoorn, Annet E M Blom, Lianne I Willems, Gijsbert A van der Marel, Herman S Overkleeft

  Organic letters. 09/2011; 13(20):5656-9.

  A series of tunable pH-dependent BODIPY dyes were synthesized and further functionalized in a Knoevenagel condensation reaction with various aldehydes. In this fashion, monofunctional dyes containingA series of tunable pH-dependent BODIPY dyes were synthesized and further functionalized in a Knoevenagel condensation reaction with various aldehydes. In this fashion, monofunctional dyes containing an alkyne, azide, or carboxylic acid (masked as its methyl ester) as ligation sites as well as asymmetrical bifunctional dyes were obtained, without compromising their pH-dependency. In addition, fluorescence excitation and emission maxima for these dyes were shown to be significantly red-shifted in comparison to their tetramethyl precursors.

• Irreversible inhibitors and activity-based probes as research tools in chemical glycobiology.

  Authors: Martin D Witte, Gijsbert A van der Marel, Johannes M F G Aerts, Herman S Overkleeft

  Organic & biomolecular chemistry. 09/2011; 9(17):5908-26.

  In this review, we will discuss the enzymes that are involved in the synthesis and degradation of glycoconjugates and we will give an overview of the inhibitors and activity-based probes (ABPs) thatIn this review, we will discuss the enzymes that are involved in the synthesis and degradation of glycoconjugates and we will give an overview of the inhibitors and activity-based probes (ABPs) that have been used to study these. Following discussion of some general aspects of the biosynthesis and degradation of N-linked glycoproteins, attention is focused on the enzymes that hydrolyze the protein-carbohydrate linkage, peptide N-glycanase and glycosylasparaginase and their mechanism. We then focus on the biosynthesis of O-linked glycoproteins and glycolipids and in particular on the enzymes that hydrolyze the interglycosidic linkages in these, the glycosidases. Some important mechanism-based glycosidase inhibitors that form a covalent bond with the targeted enzyme(s), their corresponding ABPs and their application to study this class of enzymes are highlighted. Finally, alternative pathways for degradation of glycoconjugates and an ABP-based strategy to study these will be discussed.

• Targeted pH-dependent fluorescent activity-based cathepsin probes.

  Authors: Sascha Hoogendoorn, Kim L Habets, Solène Passemard, Johan Kuiper, Gijsbert A van der Marel, Bogdan I Florea, Herman S Overkleeft

  Chemical communications (Cambridge, England). 09/2011; 47(33):9363-5.

  Bifunctional, pH-activatable BODIPY dyes were developed and incorporated in mannose cluster-containing activity-based probes for cysteine proteases. Mannose receptor-dependent uptake of the probes inBifunctional, pH-activatable BODIPY dyes were developed and incorporated in mannose cluster-containing activity-based probes for cysteine proteases. Mannose receptor-dependent uptake of the probes in dendritic cells, followed by trafficking to acidic cellular compartments resulted in fluorescence as seen by live-cell imaging, and subsequent cathepsin inhibition.

• Automated solid phase synthesis of teichoic acids.

  Authors: Wouter F J Hogendorf, Nico Meeuwenoord, Herman S Overkleeft, Dmitri V Filippov, Diana Laverde, Andrea Kropec, Johannes Huebner, Gijsbert A Van der Marel, Jeroen D C Codée

  Chemical communications (Cambridge, England). 08/2011; 47(31):8961-3.

  This communication describes the first automated solid phase synthesis of teichoic acids (TAs) and the preparation by this method of a number of well-defined TA structures, which were probed forThis communication describes the first automated solid phase synthesis of teichoic acids (TAs) and the preparation by this method of a number of well-defined TA structures, which were probed for their antigenicity. An opsonophagocytic killing assay revealed a clear TA-length-activity relationship and indicated a promising candidate for future vaccine development.

• Mannopyranosyl uronic acid donor reactivity.

  Authors: Marthe T C Walvoort, Wilbert de Witte, Jesse van Dijk, Jasper Dinkelaar, Gerrit Lodder, Herman S Overkleeft, Jeroen D C Codée, Gijsbert A van der Marel

  Organic letters. 08/2011; 13(16):4360-3.

  The reactivity of a variety of mannopyranosyl uronic acid donors was assessed in a set of competition experiments, in which two (S)-tolyl mannosyl donors were made to compete for a limited amount ofThe reactivity of a variety of mannopyranosyl uronic acid donors was assessed in a set of competition experiments, in which two (S)-tolyl mannosyl donors were made to compete for a limited amount of promoter (NIS/TfOH). These experiments revealed that the reactivity of mannuronic acid donors is significantly higher than expected based on the electron-withdrawing capacity of the C-5 carboxylic acid ester function. A 4-O-acetyl-β-(S)-tolyl mannuronic acid donor was found to have similar reactivity as per-O-benzyl-α-(S)-tolyl mannose.

• Stereoselective synthesis of 2,3-diamino-2,3-dideoxy-β-D-mannopyranosyl uronates.

  Authors: Marthe T C Walvoort, Gert-Jan Moggré, Gerrit Lodder, Herman S Overkleeft, Jeroen D C Codée, Gijsbert A van der Marel

  The Journal of organic chemistry. 08/2011; 76(18):7301-15.

  With the aim to find an efficient synthetic procedure for the construction of 2,3-diamino-2,3-dideoxy-β-D-mannuronic acids, we evaluated three mannosyl donors: (S)-phenyl 4,6-di-O-acetyl-2,3-diazidoWith the aim to find an efficient synthetic procedure for the construction of 2,3-diamino-2,3-dideoxy-β-D-mannuronic acids, we evaluated three mannosyl donors: (S)-phenyl 4,6-di-O-acetyl-2,3-diazido mannopyranoside, (S)-phenyl 2,3-diazido-4,6-O-benzylidene mannopyranoside, and (S)-phenyl 2,3-diazido mannopyranosyl methyl uronate. The first two mannosylating agents are rather unselective or slightly α-selective in their condensation with three different acceptors. The mannuronic acid donor on the other hand reliably provides the desired β-mannosidic linkage. A mechanistic rationale is put forward to account for the different behavior of the three donor types. Suitably protected 2,3-diazido mannuronic acids were employed to construct the all-cis-linked tetrasaccharide repeating unit of the capsular polysaccharide of Bacillus stearothermophilus , featuring two 2,3-diacetamido-2,3-dideoxy-β-D-mannuronic acids.

• Bioorthogonal chemistry: applications in activity-based protein profiling.

  Authors: Lianne I Willems, Wouter A van der Linden, Nan Li, Kah-Yee Li, Nora Liu, Sascha Hoogendoorn, Gijs A van der Marel, Bogdan I Florea, Herman S Overkleeft

  Accounts of chemical research. 07/2011; 44(9):718-29.

  The close interaction between organic chemistry and biology goes back to the late 18th century, when the modern natural sciences began to take shape. After synthetic organic chemistry arose as aThe close interaction between organic chemistry and biology goes back to the late 18th century, when the modern natural sciences began to take shape. After synthetic organic chemistry arose as a discipline, organic chemists almost immediately began to pursue the synthesis of naturally occurring compounds, thereby contributing to the understanding of their functions in biological processes. Research in those days was often remarkably interdisciplinary; in fact, it constituted chemical biology research before the phrase even existed. For example, histological dyes, both of an organic and inorganic nature, were developed and applied by independent researchers (Gram and Golgi) with the aim of visualizing cellular substructures (the bacterial cell wall and the Golgi apparatus). Over the years, as knowledge within the various fields of the natural sciences deepened, research disciplines drifted apart, becoming rather monodisciplinary. In these years, broadly ranging from the end of World War II to about the 1980s, organic chemistry continued to impact life sciences research, but contributions were of a more indirect nature. As an example, the development of the polymerase chain reaction, from which molecular biology and genetics research have greatly profited, was partly predicated on the availability of synthetic oligonucleotides. These molecules first became available in the late 1960s, the result of organic chemists pursuing the synthesis of DNA oligomers primarily because of the synthetic challenges involved. Today, academic natural sciences research is again becoming more interdisciplinary, and sometimes even multidisciplinary. What was termed "chemical biology" by Stuart Schreiber at the end of the last century can be roughly described as the use of intellectually chemical approaches to shed light on processes that are fundamentally rooted in biology. Chemical tools and techniques that are developed for biological studies in the exciting and rapidly evolving field of chemical biology research include contributions from many areas of the multifaceted discipline of chemistry, and particularly from organic chemistry. Researchers apply knowledge inherent to organic chemistry, such as reactivity and selectivity, to the manipulation of specific biomolecules in biological samples (cell extracts, living cells, and sometimes even animal models) to gain insight into the biological phenomena in which these molecules participate. In this Account, we highlight some of the recent developments in chemical biology research driven by organic chemistry, with a focus on bioorthogonal chemistry in relation to activity-based protein profiling. The rigorous demands of bioorthogonality have not yet been realized in a truly bioorthogonal reagent pair, but remarkable progress has afforded a range of tangible contributions to chemical biology research. Activity-based protein profiling, which aims to obtain information on the workings of a protein (or protein family) within the larger context of the full biological system, has in particular benefited from these advances. Both activity-based protein profiling and bioorthogonal chemistry have been around for approximately 15 years, and about 8 years ago the two fields very profitably intersected. We expect that each discipline, both separately and in concert, will continue to make important contributions to chemical biology research.

• Two-step bioorthogonal activity-based proteasome profiling using copper-free click reagents: a comparative study.

  Authors: Wouter A van der Linden, Nan Li, Sascha Hoogendoorn, Mark Ruben, Martijn Verdoes, Jun Guo, Geert-Jan Boons, Gijsbert A van der Marel, Bogdan I Florea, Herman S Overkleeft

  Bioorganic & medicinal chemistry. 06/2011; 20(2):662-6.

  The development and application of bioorthogonal two-step labeling techniques receives much attention. Employing bifunctional proteasome probe 2 the efficiency of two-step labeling of recentlyThe development and application of bioorthogonal two-step labeling techniques receives much attention. Employing bifunctional proteasome probe 2 the efficiency of two-step labeling of recently published biotinylated cyclooctynes 3-5 is compared to Staudinger-Bertozzi ligation in cell extracts and living cells. While cyclooctynes 3-5 react faster and at a much lower concentration then the Staudinger-Bertozzi benchmark, background labeling is considerable with these reagents.

• Ribosylation of adenosine: an orthogonally protected building block for the synthesis of ADP-ribosyl oligomers.

  Authors: Gerbrand J van der Heden van Noort, Herman S Overkleeft, Gijsbert A van der Marel, Dmitri V Filippov

  Organic letters. 06/2011; 13(11):2920-3.

  A method to ribosylate adenosine on the 2' hydroxyl function in an α-selective fashion and in good yield is presented. Protective groups chosen for the acceptor and donor used in this glycosylationA method to ribosylate adenosine on the 2' hydroxyl function in an α-selective fashion and in good yield is presented. Protective groups chosen for the acceptor and donor used in this glycosylation not only direct α-selectivity but also allow the construction of a fully orthogonally protected building block for the future assembly of oligo-ADP-ribosylated peptides and proteins.

• Synthesis and evaluation of strand and turn modified ring-extended gramicidin S derivatives.

  Authors: Annemiek D Knijnenburg, Varsha V Kapoerchan, Gijsbert M Grotenbreg, Emile Spalburg, Albert J de Neeling, Roos H Mars-Groenendijk, Daan Noort, José M Otero, Antonio L Llamas-Saiz, Mark J van Raaij, Bep Ravensbergen, Peter H Nibbering, Gijs A van der Marel, Herman S Overkleeft, Mark Overhand

  Bioorganic & medicinal chemistry. 06/2011; 19(11):3402-9.

  In this paper, we describe the crystal structure of previously reported ring-extended gramicidin S (GS) derivative 2 (GS14K4), containing a d-amino acid residue in one of the β-strand regions. ThisIn this paper, we describe the crystal structure of previously reported ring-extended gramicidin S (GS) derivative 2 (GS14K4), containing a d-amino acid residue in one of the β-strand regions. This structure is in agreement with a previously reported modeling study of the same molecule. The polar side chain of the additional d-amino acid residue is positioned at the same face of the molecule as the hydrophobic side chains, and we believe that because of this compound 2 is considerably less hydrophobic than extended GS derivatives in which the strand regions are exclusively composed of l-amino acids. Using this backbone structure as our benchmark we prepared a small series of ring-extended GS analogues featuring sugar amino acid dipeptide isosteres of varied hydrophobicity at the turn region. We show that via this approach hydrophobicity of extended GS analogues can be tuned without affecting the secondary structure (as observed from NMR and CD spectra). Biological evaluation reveals that hydrophobicity correlates to cell toxicity, but still bacteriolysis is induced with GS analogues that are too hydrophilic to efficiently lyse human red blood cells.

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• Activity-based profiling of 2-oxoglutarate oxygenases.

  Authors: Paul P Geurink, Bogdan I Florea, Herman S Overkleeft

  Chemistry & biology. 05/2011; 18(5):557-9.

  2-Oxoglutarate oxygenases (2-OGs) are a large enzyme family involved in numerous processes in health and disease. Rotili et al. (2011) describe in this issue of Chemistry & Biology an activity-based2-Oxoglutarate oxygenases (2-OGs) are a large enzyme family involved in numerous processes in health and disease. Rotili et al. (2011) describe in this issue of Chemistry & Biology an activity-based protein profiling-based strategy with which the activity of individual members of the 2-OG family can be addressed in the context of complex biological systems.

• Specific cell-permeable inhibitor of proteasome trypsin-like sites selectively sensitizes myeloma cells to bortezomib and carfilzomib.

  Authors: Anne C Mirabella, Alexandre A Pletnev, Sondra L Downey, Bogdan I Florea, Tamer B Shabaneh, Matthew Britton, Martijn Verdoes, Dmitri V Filippov, Herman S Overkleeft, Alexei F Kisselev

  Chemistry & biology. 05/2011; 18(5):608-18.

  Proteasomes degrade the majority of proteins in mammalian cells, are involved in the regulation of multiple physiological functions, and are established targets of anticancer drugs. The proteasomeProteasomes degrade the majority of proteins in mammalian cells, are involved in the regulation of multiple physiological functions, and are established targets of anticancer drugs. The proteasome has three types of active sites. Chymotrypsin-like sites are the most important for protein breakdown and have long been considered the only suitable targets for antineoplastic drugs; however, our recent work demonstrated that inhibitors of caspase-like sites sensitize malignant cells to inhibitors of the chymotrypsin-like sites. Here, we describe the development of specific cell-permeable inhibitors and an activity-based probe of the trypsin-like sites. These compounds selectively sensitize multiple myeloma cells to inhibitors of the chymotrypsin-like sites, including antimyeloma agents bortezomib and carfilzomib. Thus, trypsin-like sites are cotargets for anticancers drugs. Together with inhibitors of chymotrypsin- and caspase-like sites developed earlier, we provide the scientific community with a complete set of tools to separately modulate proteasome active sites in living cells.