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Publications

Picchianti, L.; Sanchez de Medina Hernandez, V.; Zhan, N.; Irwin, N. A.; Groh, R.; Stephani, M.; Hornegger, H.; Beveridge, R.; Sawa‐Makarska, J.; Lendl, T.; Grujic, N.; Naumann, C.; Martens, S.; Richards, T. A.; Clausen, T.; Ramundo, S.; Karagöz, G. E.; Dagdas, Y.; Shuffled ATG8 interacting motifs form an ancestral bridge between UFMylation and autophagy EMBO J. 42 e112053 (2023) DOI: 10.15252/embj.2022112053
  • Abstract
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UFMylation involves the covalent modification of substrate proteins with UFM1 (Ubiquitin-fold modifier 1) and is important for maintaining ER homeostasis. Stalled translation triggers the UFMylation of ER-bound ribosomes and activates C53-mediated autophagy to clear toxic polypeptides. C53 contains noncanonical shuffled ATG8-interacting motifs (sAIMs) that are essential for ATG8 interaction and autophagy initiation. However, the mechanistic basis of sAIM-mediated ATG8 interaction remains unknown. Here, we show that C53 and sAIMs are conserved across eukaryotes but secondarily lost in fungi and various algal lineages. Biochemical assays showed that the unicellular alga Chlamydomonas reinhardtii has a functional UFMylation pathway, refuting the assumption that UFMylation is linked to multicellularity. Comparative structural analyses revealed that both UFM1 and ATG8 bind sAIMs in C53, but in a distinct way. Conversion of sAIMs into canonical AIMs impaired binding of C53 to UFM1, while strengthening ATG8 binding. Increased ATG8 binding led to the autoactivation of the C53 pathway and sensitization of Arabidopsis thaliana to ER stress. Altogether, our findings reveal an ancestral role of sAIMs in UFMylation-dependent fine-tuning of C53-mediated autophagy activation.

Publications

Ai, H.; Bellstaedt, J.; Bartusch, K. S.; Eschen‐Lippold, L.; Babben, S.; Balcke, G. U.; Tissier, A.; Hause, B.; Andersen, T. G.; Delker, C.; Quint, M.; Auxin‐dependent regulation of cell division rates governs root thermomorphogenesis EMBO J. 42 e111926 (2023) DOI: 10.15252/embj.2022111926
  • Abstract
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Roots are highly plastic organs enabling plants to adapt to a changing below-ground environment. In addition to abiotic factors like nutrients or mechanical resistance, plant roots also respond to temperature variation. Below the heat stress threshold, Arabidopsis thaliana seedlings react to elevated temperature by promoting primary root growth, possibly to reach deeper soil regions with potentially better water saturation. While above-ground thermomorphogenesis is enabled by thermo-sensitive cell elongation, it was unknown how temperature modulates root growth. We here show that roots are able to sense and respond to elevated temperature independently of shoot-derived signals. This response is mediated by a yet unknown root thermosensor that employs auxin as a messenger to relay temperature signals to the cell cycle. Growth promotion is achieved primarily by increasing cell division rates in the root apical meristem, depending on de novo local auxin biosynthesis and temperature-sensitive organization of the polar auxin transport system. Hence, the primary cellular target of elevated ambient temperature differs fundamentally between root and shoot tissues, while the messenger auxin remains the same.

Publications

Zanatta, N.; Mittersteiner, M.; Aquino, E. C.; Budragchaa, T.; Wessjohann, L. A.; Bonacorso, H. G.; Martins, M. A. P.; Synthesis of methylene-bridged trifluoromethyl azoles using 5-(1,2,3-Triazol-1-yl)enones Synthesis 54 439-450 (2022) DOI: 10.1055/s-0040-1719837
  • Abstract
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A protocol for synthesizing triazole-containing pyrazolines and pyrazoles selectively using trifluoromethylated 5-(1,2,3-triazol-1-yl)enones as starting materials, is reported. The selectivity of the reaction was controlled by the nature of the hydrazine or derivative used: free hydrazines furnished the 1,5-regiosiomer exclusively in yields up to 98%, whereas protected hydrazines provided the 1,3-regioisomer in yields up to 77%. To demonstrate the synthetic versatility of the triazole-based enone, reactions with other unsymmetrical dinucleophiles (hydroxylamine hydrochloride and S-methyl isothiourea sulfates) allowed the selective preparation of triazole-containing isoxazoline and pyrimidine rings.

Publications

Bagchi, R.; Melnyk, C. W.; Christ, G.; Winkler, M.; Kirchsteiner, K.; Salehin, M.; Mergner, J.; Niemeyer, M.; Schwechheimer, C.; Calderón Villalobos, L. I. A.; Estelle, M.; The Arabidopsis ALF4 protein is a regulator of SCF E3 ligases EMBO J. 37 255-268 (2018) DOI: 10.15252/embj.201797159
  • Abstract
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The cullin‐RING E3 ligases (CRLs) regulate diverse cellular processes in all eukaryotes. CRL activity is controlled by several proteins or protein complexes, including NEDD8, CAND1, and the CSN. Recently, a mammalian protein called Glomulin (GLMN) was shown to inhibit CRLs by binding to the RING BOX (RBX1) subunit and preventing binding to the ubiquitin‐conjugating enzyme. Here, we show that Arabidopsis ABERRANT LATERAL ROOT FORMATION4 (ALF4) is an ortholog of GLMN. The alf4 mutant exhibits a phenotype that suggests defects in plant hormone response. We show that ALF4 binds to RBX1 and inhibits the activity of SCFTIR1, an E3 ligase responsible for degradation of the Aux/IAA transcriptional repressors. In vivo, the alf4 mutation destabilizes the CUL1 subunit of the SCF. Reduced CUL1 levels are associated with increased levels of the Aux/IAA proteins as well as the DELLA repressors, substrate of SCFSLY1. We propose that the alf4 phenotype is partly due to increased levels of the Aux/IAA and DELLA proteins.

Publications

Gulyas-Fekete, G.; Boluda, C. J.; Westermann, B.; Wessjohann, L. A.; Anti-Friedel-Crafts-Type Substitution To Form Biaryl Linkages Synthesis 45 3038-3043 (2013) DOI: 10.1055/s-0033-1339682
  • Abstract
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The ipso-substitution of one (or two) hydroxy groups of phloroglucinol with arene nucleophiles (e.g., o-xylene, tetralin, biphenyl) can be achieved easily under Friedel–Crafts-type conditions with or without the use of organic solvents affording a variety of 3,5-dihydroxybiphenyls (57–89% yields). The new method has significant practical advantages compared to classical biaryl-­coupling routes.

Publications

Wouters, A. D.; Bessa, A. B.; Sachini, M.; Wessjohann, L. A.; Lüdtke, D. S.; Boron-Zinc Exchange in The Diastereoselective Arylation of Sugar-Based Aldehydes­: Stereoselective Synthesis of (+)-7-epi-Goniofufurone and Analogues Synthesis 45 2222-2233 (2013) DOI: 10.1055/s-0033-1339285
  • Abstract
  • BibText
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The substrate-controlled diastereoselective arylation of chiral aldehydes readily available from carbohydrates is described, using the boron–zinc exchange reaction to generate the transferable aryl groups. The methodology developed was applied to the total synthesis of the styryllactone (+)-7-epi-goniofufurone and analogues thereof.

Publications

Henze, M.; Kreye, O.; Brauch, S.; Nitsche, C.; Naumann, K.; Wessjohann, L. A.; Westermann, B.; Photoaffinity-Labeled Peptoids and Depsipeptides by Multicomponent Reactions Synthesis 2010 2997-3003 (2010) DOI: 10.1055/s-0030-1258182
  • Abstract
  • BibText
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Photoaffinity tags can be incorporated easily into peptoids and congeners by the Ugi and Passerini multicomponent reactions. Products related to photo-methionine and photo-leucine can be accomplished by diazirine-containing building blocks. The same protocols can be used to synthesize derivatives with benzophenone photo cross-linkers.

Publications

Braga, A. L.; Wessjohann, L. A.; Taube, P. S.; Galetto, F. Z.; de Andrade, F. M.; Straightforward Method for the Synthesis of Selenocysteine and Selenocystine Derivatives from L-Serine Methyl Ester Synthesis 2010 3131-3137 (2010) DOI: 10.1055/s-0030-1258188
  • Abstract
  • BibText
  • RIS

A set of selenoamino acids has been efficiently synthesized under smooth conditions by a simple, flexible and modular strategy. In this method, O-mesylated l-serine methyl ester is generated in situ and directly substituted with various selenolate anions to afford selenocysteine, selenolanthionine, and selenocystine derivatives in good yields. Also, a tellurocysteine derivative can be obtained by this method.

Publications

Bohn Rhoden, C. R.; Westermann, B.; Wessjohann, L.; One-Pot Multicomponent Synthesis of N-Substituted Tryptophan-Derived Diketopiperazines Synthesis 2008 2077-2082 (2008) DOI: 10.1055/s-2008-1067112
  • Abstract
  • BibText
  • RIS

A simple, rapid, one-pot multicomponent synthesis of tryptophan-derived diketopiperazines with variable side chains is presented. Microwave radiation gives comparable yields, but allows a significant decrease in reaction times.

Publications

de Greef, M.; Abeln, S.; Belkasmi, K.; Dömling, A.; Orru, R.; Wessjohann, L.; Rapid Combinatorial Access to Macrocyclic Ansapeptoids and Ansapeptides with Natural-Product-like Core Structures Synthesis 2006 3997-4004 (2006) DOI: 10.1055/s-2006-950335
  • Abstract
  • BibText
  • RIS

14-Membered ansa-cyclopeptide alkaloids are among the most abundant natural macrocycles and thus valuable templates for diversity-oriented synthesis with biological relevance. A rapid synthesis of the core structure is conceivable by a combination of an Ugi four-component reaction with bifunctional building blocks to form the dipeptoid part, followed by a suitable macrocyclization reaction. The latter step is crucial, and an uncommon macroetherification gave the best results. The use of ammonium salts allows direct access to peptides instead of peptoids. Depending on the substitution pattern, some cyclopeptoids show planar chirality despite free rotation of the phenylene group.

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