Herzig, Alf

[["dc.bibliographiccitation.artnumber","e24701"],["dc.bibliographiccitation.issue","9"],["dc.bibliographiccitation.journal","PLoS ONE"],["dc.bibliographiccitation.volume","6"],["dc.contributor.author","Balija, Madhu Babu Gajula"],["dc.contributor.author","Griesinger, Christian"],["dc.contributor.author","Herzig, Alf"],["dc.contributor.author","Zweckstetter, Markus"],["dc.contributor.author","Jaeckle, Herbert"],["dc.date.accessioned","2017-09-07T11:43:24Z"],["dc.date.available","2017-09-07T11:43:24Z"],["dc.date.issued","2011"],["dc.description.abstract","Parkinson's disease (PD) is linked to the formation of insoluble fibrillar aggregates of the presynaptic protein alpha-Synuclein (alpha S) in neurons. The appearance of such aggregates coincides with severe motor deficits in human patients. These deficits are often preceded by non-motor symptoms such as sleep-related problems in the patients. PD-like motor deficits can be recapitulated in model organisms such as Drosophila melanogaster when alpha S is pan-neurally expressed. Interestingly, both these deficits are more severe when alpha S mutants with reduced aggregation properties are expressed in flies. This indicates that that alpha S aggregation is not the primary cause of the PD-like motor symptoms. Here we describe a model for PD in Drosophila which utilizes the targeted expression of alpha S mutants in a subset of dopadecarboxylase expressing serotonergic and dopaminergic (DA) neurons. Our results show that targeted expression of pre-fibrillar alpha S mutants not only recapitulates PD-like motor symptoms but also the preceding non-motor symptoms such as an abnormal sleep-like behavior, altered locomotor activity and abnormal circadian periodicity. Further, the results suggest that the observed non-motor symptoms in flies are caused by an early impairment of neuronal functions rather than by the loss of neurons due to cell death."],["dc.identifier.doi","10.1371/journal.pone.0024701"],["dc.identifier.gro","3142669"],["dc.identifier.isi","000294802800085"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/98"],["dc.notes.intern","WoS Import 2017-03-10 / Funder: Max-Planck-Society"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Public Library Science"],["dc.relation.issn","1932-6203"],["dc.title","Pre-Fibrillar alpha-Synuclein Mutants Cause Parkinson's Disease-Like Non-Motor Symptoms in Drosophila"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1634"],["dc.bibliographiccitation.issue","10"],["dc.bibliographiccitation.journal","European Journal of Organic Chemistry"],["dc.bibliographiccitation.lastpage","1645"],["dc.contributor.author","Tietze, Lutz Friedjan"],["dc.contributor.author","Herzig, T."],["dc.contributor.author","Feuerstein, T."],["dc.contributor.author","Schuberth, I."],["dc.date.accessioned","2018-11-07T10:30:10Z"],["dc.date.available","2018-11-07T10:30:10Z"],["dc.date.issued","2002"],["dc.description.abstract","This paper describes novel seco-analogues 25-27 of the cytotoxic antibiotic CC-1065 (1) and their prodrugs 5, 6a, and 6b, for antibody-directed enzyme prodrug therapy (ADEPT), The partially hydrogenated seco-CCI-analogue 7 and the corresponding methyl-CCI analogues 8a and 8b were synthesized by alkylation of 9 with 15 and 16, respectively, followed by radical cyclization and deprotection. Treatment of 7, 8a, and 8b with the galactose trichloroacetimidate 21 and the bisindolyl-carboxylic acid 20 in the presence of EDC followed by solvolysis gave the desired prodrugs 5, 6a, and 6b, respectively, Compounds 25-27 were prepared by treatment of 7, 8a, and 8b with 20 after deprotection, In vitro tests showed a strong cytotoxicity for 25 and a fairly low toxicities for 26 and 27. However, the selectivity of the prodrugs 5, 6a, and 6b was not sufficient for ADEPT, Interestingly, 8a and 8b did not undergo Winstein cyclization to produce the spirocyclopropylcyclohexadienone moiety. (C) Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002."],["dc.identifier.isi","000175636300006"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/43808"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-v C H Verlag Gmbh"],["dc.relation.issn","1434-193X"],["dc.title","Synthesis and biological evaluation of novel analogues and prodrugs of the cytotoxic antibiotic CC-1065 for selective cancer therapy"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","27989"],["dc.bibliographiccitation.issue","36"],["dc.bibliographiccitation.journal","Journal of Biological Chemistry"],["dc.bibliographiccitation.lastpage","27999"],["dc.bibliographiccitation.volume","275"],["dc.contributor.author","Herzig, S."],["dc.contributor.author","Fuzesi, Laszlo"],["dc.contributor.author","Knepel, Willhart"],["dc.date.accessioned","2018-11-07T10:17:09Z"],["dc.date.available","2018-11-07T10:17:09Z"],["dc.date.issued","2000"],["dc.description.abstract","Homeodomain proteins specify developmental pathways and cell-specific gene transcription whereby proteins of the PBC subclass can direct target gene specificity of Hox proteins. Proteins encoded by nonclustered homeobox genes have been shown to be essential for cell lineage differentiation and gene expression in pancreatic islets. Using specific antiserum in an electrophoretic mobility shift assay and in vitro transcribed/ translated proteins, the nuclear proteins binding domain B of the G3 enhancer-like element of the glucagon gene were identified in the present study as heterodimers consisting of the ubiquitously expressed homeodomain protein Prep1 and the also widely expressed PBC homeoprotein Pbx (isoform 1a, 1b, or 2), These heterodimeric complexes were found to bind also to the glucagon cAMP response element and to a newly identified element termed G5 (from -169 to -140). Whereas the expression of Prep1 or Pbx forms alone had no effect, coexpression of Pbx1a/1b-Prep1 inhibited the glucagon promoter when activated by cotransfected Pax6 or another transcription factor in non-glucagon-producing cells. In contrast, in glucagon-producing pancreatic islet cells, Pbx-Prep1 had no effect on GAL4-Pax6-induced mutant glucagon promoter activity or on Pax6-dependent wild-type glucagon promoter activity. Furthermore, 5'-deletion of G5 enhanced glucagon promoter activity in a non-glucagon producing cell line but not in glucagon-producing islet cells. This study thus identifies a novel target and Hox-independent function of Pbx-Prep1 heterodimers that, through repression of glucagon gene transcription in non-glucagon-producing cells, may help to establish islet cell-specific expression of the glucagon gene."],["dc.identifier.isi","000089197100063"],["dc.identifier.pmid","10869353"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/41178"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Soc Biochemistry Molecular Biology Inc"],["dc.relation.issn","0021-9258"],["dc.title","Heterodimeric Pbx-Prep1 homeodomain protein binding to the glucagon gene restricting transcription in a cell type-dependent manner"],["dc.type","review"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","3256"],["dc.bibliographiccitation.issue","20"],["dc.bibliographiccitation.journal","EMBO Journal"],["dc.bibliographiccitation.lastpage","3268"],["dc.bibliographiccitation.volume","28"],["dc.contributor.author","Karpinar, Damla Pinar"],["dc.contributor.author","Balija, Madhu Babu Gajula"],["dc.contributor.author","Kügler, Sebastian"],["dc.contributor.author","Opazo, Felipe"],["dc.contributor.author","Rezaei-Ghaleh, Nasrollah"],["dc.contributor.author","Wender, Nora"],["dc.contributor.author","Kim, Hai-Young"],["dc.contributor.author","Taschenberger, Grit"],["dc.contributor.author","Falkenburger, Bjoern H."],["dc.contributor.author","Heise, Henrike"],["dc.contributor.author","Kumar, Ashutosh"],["dc.contributor.author","Riedel, Dietmar"],["dc.contributor.author","Fichtner, Lars"],["dc.contributor.author","Voigt, Aaron"],["dc.contributor.author","Braus, Gerhard H."],["dc.contributor.author","Giller, Karin"],["dc.contributor.author","Becker, Stefan"],["dc.contributor.author","Herzig, Alf"],["dc.contributor.author","Baldus, Marc"],["dc.contributor.author","Jaeckle, Herbert"],["dc.contributor.author","Eimer, Stefan"],["dc.contributor.author","Schulz, Joerg B."],["dc.contributor.author","Griesinger, Christian"],["dc.contributor.author","Zweckstetter, Markus"],["dc.date.accessioned","2017-09-07T11:46:48Z"],["dc.date.available","2017-09-07T11:46:48Z"],["dc.date.issued","2009"],["dc.description.abstract","The relation of alpha-synuclein (alpha S) aggregation to Parkinson's disease (PD) has long been recognized, but the mechanism of toxicity, the pathogenic species and its molecular properties are yet to be identified. To obtain insight into the function different aggregated alpha S species have in neurotoxicity in vivo, we generated alpha S variants by a structure-based rational design. Biophysical analysis revealed that the alpha S mutants have a reduced fibrillization propensity, but form increased amounts of soluble oligomers. To assess their biological response in vivo, we studied the effects of the biophysically defined pre-fibrillar alpha S mutants after expression in tissue culture cells, in mammalian neurons and in PD model organisms, such as Caenorhabditis elegans and Drosophila melanogaster. The results show a striking correlation between alpha S aggregates with impaired beta-structure, neuronal toxicity and behavioural defects, and they establish a tight link between the biophysical properties of multimeric aS species and their in vivo function. The EMBO Journal (2009) 28, 3256-3268. doi:10.1038/emboj.2009.257; Published online 10 September 2009"],["dc.identifier.doi","10.1038/emboj.2009.257"],["dc.identifier.gro","3143038"],["dc.identifier.isi","000271008200017"],["dc.identifier.pmid","19745811"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/508"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Nature Publishing Group"],["dc.relation.issn","0261-4189"],["dc.title","Pre‐fibrillar α‐synuclein variants with impaired β‐structure increase neurotoxicity in Parkinson's disease models"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","562"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","European Journal of Organic Chemistry"],["dc.bibliographiccitation.lastpage","566"],["dc.contributor.author","Tietze, Lutz Friedjan"],["dc.contributor.author","Haunert, F."],["dc.contributor.author","Feuerstein, T."],["dc.contributor.author","Herzig, T."],["dc.date.accessioned","2018-11-07T10:41:14Z"],["dc.date.available","2018-11-07T10:41:14Z"],["dc.date.issued","2003"],["dc.description.abstract","A short and efficient synthesis of seco-duocarmycin SA (3), a highly potent cytostatic agent and direct precursor of the natural product duocarmycin SA (1), has been achieved. Starting from commercially available 2-methoxy-4-nitroaniline (4) the synthetic protocol contains a Fischer indole synthesis to introduce the heterocyclic scaffold and a radical 5-exo-trig cyclization to furnish the (chloromethyl)indoline ring system as key reactions. ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)."],["dc.identifier.isi","000180805100021"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/46488"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-v C H Verlag Gmbh"],["dc.relation.issn","1434-193X"],["dc.title","A concise and efficient synthesis of seco-duocarmycin SA"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e15567"],["dc.bibliographiccitation.journal","eLife"],["dc.bibliographiccitation.volume","5"],["dc.contributor.author","Schnorrenberg, Sebastian"],["dc.contributor.author","Grotjohann, Tim"],["dc.contributor.author","Vorbrüggen, Gerd"],["dc.contributor.author","Herzig, Alf"],["dc.contributor.author","Hell, Stefan W."],["dc.contributor.author","Jakobs, Stefan"],["dc.date.accessioned","2020-12-10T18:48:05Z"],["dc.date.available","2020-12-10T18:48:05Z"],["dc.date.issued","2016"],["dc.description.abstract","Despite remarkable developments in diffraction unlimited super-resolution microscopy, in vivo nanoscopy of tissues and model organisms is still not satisfactorily established and rarely realized. RESOLFT nanoscopy is particularly suited for live cell imaging because it requires relatively low light levels to overcome the diffraction barrier. Previously, we introduced the reversibly switchable fluorescent protein rsEGFP2, which facilitated fast RESOLFT nanoscopy (Grodohann et al., 2012). In that study, as in most other nanoscopy studies, only cultivated single cells were analyzed. Here, we report on the use of rsEGFP2 for live-cell RESOLFT nanoscopy of sub-cellular structures of intact Drosophila melanogaster larvae and of resected tissues. We generated flies expressing fusion proteins of alpha-tubulin and rsEGFP2 highlighting the microtubule cytoskeleton in all cells. By focusing through the intact larval cuticle, we achieved lateral resolution of <60 nm. RESOLFT nanoscopy enabled time-lapse recordings comprising 40 images and facilitated recordings 40 ism deep within fly tissues."],["dc.identifier.doi","10.7554/eLife.15567"],["dc.identifier.eissn","2050-084X"],["dc.identifier.fs","626317"],["dc.identifier.gro","3141660"],["dc.identifier.isi","000379856900001"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/13549"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/79008"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","2050-084X"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","In vivo super-resolution RESOLFT microscopy of Drosophila melanogaster"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","758"],["dc.bibliographiccitation.issue","10"],["dc.bibliographiccitation.journal","ChemBioChem"],["dc.bibliographiccitation.lastpage","765"],["dc.bibliographiccitation.volume","2"],["dc.contributor.author","Tietze, Lutz Friedjan"],["dc.contributor.author","Herzig, T."],["dc.contributor.author","Fecher, A."],["dc.contributor.author","Haunert, F."],["dc.contributor.author","Schuberth, I."],["dc.date.accessioned","2018-11-07T08:33:50Z"],["dc.date.available","2018-11-07T08:33:50Z"],["dc.date.issued","2001"],["dc.description.abstract","Novel prodrugs of the cytotoxic antibiotic CC-1065 for an antibody directed enzyme prodrug therapy (ADEPT) were prepared that show an excellent selectivity with a high toxicity of the corresponding drug. In particular,a the seco-CBI analogue of CC-1065, 1-chloromethyl-5-hydroxy-1,2-dihydro-3H-benz[e]indole as well as the novel methyl-seco-CBI analogue 1-(1'-chloroethyl)-5-hydroxy-1,2-dihydro-3H-benz[e]indole, were synthesized and transformed into their galactosides 10a and 10b, respectively. These galactosides can be cleaved with beta -D-galactosidase to give the free cytoxic compounds. They were tested in in vitro cytotoxicity assays by using human bronchial carcinoma cells of line A549 in the presence and in the absence of beta -D-galactosidase. While the seco-CBI prodrugs revealed only modest selectivity, prodrugs of the methyl-seco-CBI analogue bearing an anti orientation of the substituents at the two stereogenic centers of the N-heterocycle displayed an excellent selectivity with an ED50 quotient of about 750. The cytotoxicity of the corresponding phenol was rather high, with an ED50 of 1.3 nM. The diastereomer with a syn orientation at the stereogenic centers was much less toxic."],["dc.identifier.doi","10.1002/1439-7633(20011001)2:10<758::AID-CBIC758>3.0.CO;2-G"],["dc.identifier.isi","000171410000006"],["dc.identifier.pmid","11948858"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/17684"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-v C H Verlag Gmbh"],["dc.relation.issn","1439-4227"],["dc.title","Highly selective glycosylated prodrugs of cytostatic CC-1065 analogues for antibody-directed enzyme tumor therapy"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1929"],["dc.bibliographiccitation.issue","7"],["dc.bibliographiccitation.journal","Bioorganic & Medicinal Chemistry"],["dc.bibliographiccitation.lastpage","1939"],["dc.bibliographiccitation.volume","9"],["dc.contributor.author","Tietze, Lutz Friedjan"],["dc.contributor.author","Lieb, M."],["dc.contributor.author","Herzig, T."],["dc.contributor.author","Haunert, F."],["dc.contributor.author","Schuberth, I."],["dc.date.accessioned","2018-11-07T08:53:54Z"],["dc.date.available","2018-11-07T08:53:54Z"],["dc.date.issued","2001"],["dc.description.abstract","Immuno-conjugates obtained by linking enzymes with appropriate monoclonal antibodies, which bind to tumor-associated antigens, can be employed in a tumor-selective antibody directed enzyme prodrug therapy (ADEPT). For this strategy the glycosides 17a-c were prepared as prodrugs of CI-TMI 14 which is a structurally simplified analogue of the highly potent antitumor agent duocarmycin SA 2. Exposure of 17a-c to cultured carcinoma cells of line A549 displayed a very low toxicity; however, after addition of the corresponding enzymes and exposure for 24 h at prodrug concentrations of <0.1 M the proliferation of the carcinoma cells was inhibited almost completely with ED50prodrug/ED50drug of UP to 270 in the presence and in the absence of the enzyme. The synthesis of 17a-c was achieved by transformation of nitroanisidine 6 into 12 which was glycosidated to give 16a-c. Removal of the silyl groups, introduction of a chlorine atom and solvolysis of the acetal groups led to 17a-c, of which 17a and 17c are promising candidates for further elaboration. (C) 2001 Elsevier Science Ltd. All rights reserved."],["dc.identifier.doi","10.1016/S0968-0896(01)00098-0"],["dc.identifier.isi","000169580500033"],["dc.identifier.pmid","11425596"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/22537"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Pergamon-elsevier Science Ltd"],["dc.relation.issn","0968-0896"],["dc.title","A strategy for tumor-selective chemotherapy by enzymatic liberation of seco-duocarmycin SA-derivatives from nontoxic prodrugs"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]