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Dive into the research topics where Alexander Heckel is active.

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Featured researches published by Alexander Heckel.


Angewandte Chemie | 2012

Light-controlled tools.

Clara Brieke; Falk Rohrbach; Alexander Gottschalk; Guenter Mayer; Alexander Heckel

Spatial and temporal control over chemical and biological processes plays a key role in life, where the whole is often much more than the sum of its parts. Quite trivially, the molecules of a cell do not form a living system if they are only arranged in a random fashion. If we want to understand these relationships and especially the problems arising from malfunction, tools are necessary that allow us to design sophisticated experiments that address these questions. Highly valuable in this respect are external triggers that enable us to precisely determine where, when, and to what extent a process is started or stopped. Light is an ideal external trigger: It is highly selective and if applied correctly also harmless. It can be generated and manipulated with well-established techniques, and many ways exist to apply light to living systems--from cells to higher organisms. This Review will focus on developments over the last six years and includes discussions on the underlying technologies as well as their applications.


Nature Nanotechnology | 2010

A double-stranded DNA rotaxane

Damian Ackermann; Thorsten Schmidt; Jeffrey S. Hannam; Chandra Shekhar Purohit; Alexander Heckel; Michael Famulok

Mechanically interlocked molecules such as rotaxanes and catenanes have potential as components of molecular machinery. Rotaxanes consist of a dumb-bell-shaped molecule encircled by a macrocycle that can move unhindered along the axle, trapped by bulky stoppers. Previously, rotaxanes have been made from a variety of molecules, but not from DNA. Here, we report the design, assembly and characterization of rotaxanes in which both the dumb-bell-shaped molecule and the macrocycle are made of double-stranded DNA, and in which the axle of the dumb-bell is threaded through the macrocycle by base pairing. The assembly involves the formation of pseudorotaxanes, in which the macrocycle and the axle are locked together by hybridization. Ligation of stopper modules to the axle leads to the characteristic dumb-bell topology. When an oligonucleotide is added to release the macrocycle from the axle, the pseudorotaxanes are either converted to mechanically stable rotaxanes, or they disassemble by means of a slippage mechanism to yield a dumb-bell and a free macrocycle. Our DNA rotaxanes allow the fields of mechanically interlocked molecules and DNA nanotechnology to be combined, thus opening new possibilities for research into molecular machines and synthetic biology.


Nano Letters | 2011

Construction of a structurally defined double-stranded DNA catenane.

Thorsten Schmidt; Alexander Heckel

Topologically interlocked structures like catenanes and rotaxanes are promising components for the construction of molecular machines and motors. Herein we describe the construction of double-stranded DNA catenanes for DNA nanotechnology. For this, C-shaped DNA minicircle fragments were equipped with sequence-specific DNA-binding polyamides and their respective binding site. Formation of catenanes is achieved by self-assembly of two of these fragments and subsequent addition of a ring-closing oligonucleotide.


Angewandte Chemie | 2000

Immobilization of TADDOL with a High Degree of Loading on Porous Silica Gel and First Applications in Enantioselective Catalysis.

Alexander Heckel; Dieter Seebach

The versatile TADDOL moiety has been immobilized for the first time on an inorganic support (highly porous silica gel). This gives access to Ti - Lewis acids (see picture), which turn out to be very efficient in two standard enantioselective reactions. X=OiPr, OTos.


Nucleic Acids Research | 2011

The Bowen–Conradi syndrome protein Nep1 (Emg1) has a dual role in eukaryotic ribosome biogenesis, as an essential assembly factor and in the methylation of Ψ1191 in yeast 18S rRNA

Britta Meyer; Jan Philip Wurm; Peter Kötter; Matthias S. Leisegang; Valeska Schilling; Markus Buchhaupt; Martin Held; Ute Bahr; Michael Karas; Alexander Heckel; Markus T. Bohnsack; Jens Wöhnert; Karl-Dieter Entian

The Nep1 (Emg1) SPOUT-class methyltransferase is an essential ribosome assembly factor and the human Bowen–Conradi syndrome (BCS) is caused by a specific Nep1D86G mutation. We recently showed in vitro that Methanocaldococcus jannaschii Nep1 is a sequence-specific pseudouridine-N1-methyltransferase. Here, we show that in yeast the in vivo target site for Nep1-catalyzed methylation is located within loop 35 of the 18S rRNA that contains the unique hypermodification of U1191 to 1-methyl-3-(3-amino-3-carboxypropyl)-pseudouri-dine (m1acp3Ψ). Specific 14C-methionine labelling of 18S rRNA in yeast mutants showed that Nep1 is not required for acp-modification but suggested a function in Ψ1191 methylation. ESI MS analysis of acp-modified Ψ-nucleosides in a Δnep1-mutant showed that Nep1 catalyzes the Ψ1191 methylation in vivo. Remarkably, the restored growth of a nep1-1ts mutant upon addition of S-adenosylmethionine was even observed after preventing U1191 methylation in a Δsnr35 mutant. This strongly suggests a dual Nep1 function, as Ψ1191-methyltransferase and ribosome assembly factor. Interestingly, the Nep1 methyltransferase activity is not affected upon introduction of the BCS mutation. Instead, the mutated protein shows enhanced dimerization propensity and increased affinity for its RNA-target in vitro. Furthermore, the BCS mutation prevents nucleolar accumulation of Nep1, which could be the reason for reduced growth in yeast and the Bowen-Conradi syndrome.


ChemBioChem | 2005

Light‐Induced Formation of G‐Quadruplex DNA Secondary Structures

Günter Mayer; Lenz Kröck; Vera Mikat; Marianne Engeser; Alexander Heckel

The attachment of photolabile “protecting” groups to mask the activity of biologically active compounds is commonly referred to as “caging”. The active molecule can be released by irradiation with the laser of a confocal microscope. The method provides exact control over the location, dose and time at which this event occurs. The strengths of this approach lie, for example, in the arbitrary choice of location where a pro-


Nucleic Acids Research | 2010

The ribosome assembly factor Nep1 responsible for Bowen–Conradi syndrome is a pseudouridine-N1-specific methyltransferase

Jan Philip Wurm; Britta Meyer; Ute Bahr; Martin Held; Olga Frolow; Peter Kötter; Joachim W. Engels; Alexander Heckel; Michael Karas; Karl-Dieter Entian; Jens Wöhnert

Nep1 (Emg1) is a highly conserved nucleolar protein with an essential function in ribosome biogenesis. A mutation in the human Nep1 homolog causes Bowen–Conradi syndrome—a severe developmental disorder. Structures of Nep1 revealed a dimer with a fold similar to the SPOUT-class of RNA-methyltransferases suggesting that Nep1 acts as a methyltransferase in ribosome biogenesis. The target for this putative methyltransferase activity has not been identified yet. We characterized the RNA-binding specificity of Methanocaldococcus jannaschii Nep1 by fluorescence- and NMR-spectroscopy as well as by yeast three-hybrid screening. Nep1 binds with high affinity to short RNA oligonucleotides corresponding to nt 910–921 of M. jannaschii 16S rRNA through a highly conserved basic surface cleft along the dimer interface. Nep1 only methylates RNAs containing a pseudouridine at a position corresponding to a previously identified hypermodified N1-methyl-N3-(3-amino-3-carboxypropyl) pseudouridine (m1acp3-Ψ) in eukaryotic 18S rRNAs. Analysis of the methylated nucleoside by MALDI-mass spectrometry, HPLC and NMR shows that the methyl group is transferred to the N1 of the pseudouridine. Thus, Nep1 is the first identified example of an N1-specific pseudouridine methyltransferase. This enzymatic activity is also conserved in human Nep1 suggesting that Nep1 is the methyltransferase in the biosynthesis of m1acp3-Ψ in eukaryotic 18S rRNAs.


Journal of the American Chemical Society | 2012

Ultrafast dynamics of a spiropyran in water.

Jörg Kohl-Landgraf; Markus Braun; Cem Özçoban; Diana P. N. Gonçalves; Alexander Heckel; Josef Wachtveitl

The reversible switching of a water-soluble spiropyran compound is recorded over 1 ns by means of femtosecond vis-pump/vis- and IR-probe spectroscopy under aqueous conditions. Our investigations reveal that the photochemical conversion from the closed spiropyran to the open merocyanine takes 1.6 ps whereas the reversed photoreaction is accomplished within 25 ps. The combination of time-resolved and steady-state observations allows us to reveal central parts of the reaction pathway leading to either form. The enhanced water solubility, its fast and efficient switching behavior, and its stability against hydrolysis over a time range of several weeks make this compound an attractive and versatile tool for biological applications.


ChemBioChem | 2009

Differential Regulation of Protein Subdomain Activity with Caged Bivalent Ligands

Günter Mayer; Jens Müller; Timo Mack; Daniel F. Freitag; Thomas Höver; Bernd Pötzsch; Alexander Heckel

Subtle change: Spatiotemporal modulation of individual protein subdomains with light as the trigger signal becomes possible by using bivalent aptamers and introducing photolabile “caging groups” to switch individual aptamer modules ON or OFF differentially. To the best of our knowledge, this is the first study to show that it is possible to modulate individual domain activity in aptamers, and thus also domain activity in proteins, with light.


Chemistry: A European Journal | 2002

Preparation and characterization of TADDOLs immobilized on hydrophobic controlled-pore-glass silica gel and their use in enantioselective heterogeneous catalysis.

Alexander Heckel; Dieter Seebach

Highly porous silica gel (controlled-pore glass, CPG, ca. 300 m2 g(-1)) with covalently attached TADDOLs (loading 0.3-0.4 mmol g(-1)) and Me3Si-hydrophobized surface has been prepared: First, mercaptopropyl groups were attached to the silica gel by treatment with (mercaptopropyl)trimethoxysilane; then the SH groups were trityl-protected, and the remaining accessible SiOH groups hydrophobized by silylation (heating with Me3Si-imidazole); after deprotection, the SH groups were used as nucleophiles for benzylation with TADDOLs carrying a 4-bromomethyl-phenyl group in the 2-position of their dioxolane rings; alternatively, the SH groups have been benzylated with the 4-bromomethyl-benzaldehyde acetal of diethyltartrate, and the diarylmethanol moieties of the TADDOLs created on the solid support by addition of excess phenyl, or 1- or 2-naphthyl magnesium bromide. Each step of the immobilizing procedure was carefully monitored and analyzed (Ellmans test, methyl-red test), and resulting materials characterized by electron microscopy, DRIFT spectroscopy (IR), 13C- and 29Si NMR solid-state NMR spectroscopy, and elemental analysis. The immobilized TADDOLs were titanated to give (iPrO)2Ti-, Cl2Ti-, or (TosO)2Ti-TADDOLates which were used for catalyzing the additions of Et2Zn or Bu2Zn to PhCHO and of diphenyl nitrone to 3-crotonoyl-oxazolidinone. The following findings are remarkable: i) The enantioselectivities and conversions of the reactions mediated by the CPG-immobilized Ti-TADDOLates match those observed under standard homogeneous conditions. ii) If and when the rates and/or the enantioselectivities of reactions have dropped after several applications of the same catalyst batch, washing with aqueous HCl/acetone and reloading with titanate leads to full restoration of its performance. iii) There is no detectable loss of the hydrophobizing Me3Si groups after nine acidic washes! iv) There is a seasoning of the catalyst material in the Cl2Ti-TADDOLate-mediated [3+2] cycloaddition of diphenylnitrone: Initially it is necessary to use 0.5 equivalents of the immobilized catalyst to match the performance of the homogeneous catalyst; after three runs the reaction rate, enantio- and diastereoselectivity have dropped considerably; acidic washing after each subsequent run completely restores the performance; after a total of seven runs the amount of catalyst can be reduced to 0.4, 0.3, 0.2, and 0.1 equivalents in the following runs, with identical good results!

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Josef Wachtveitl

Goethe University Frankfurt

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Thorsten Schmidt

Dresden University of Technology

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Florian Schäfer

Goethe University Frankfurt

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Harald Schwalbe

Goethe University Frankfurt

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Tatjana Stoess

Goethe University Frankfurt

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Robert Tampé

Goethe University Frankfurt

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Volker Gatterdam

Goethe University Frankfurt

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