The Experts below are selected from a list of 114 Experts worldwide ranked by ideXlab platform
Jurgen Rohr - One of the best experts on this subject based on the ideXlab platform.
-
how mithramycin stereochemistry dictates its structure and dna binding function
MedChemComm, 2019Co-Authors: Caixia Hou, Jurgen Rohr, Sean Parkin, Oleg V TsodikovAbstract:An Aureolic Acid natural product mithramycin (MTM) has been known for its potent antineoplastic properties. MTM inhibits cell growth by binding in the minor groove of double-stranded DNA as a dimer, in which the two molecules of MTM are coordinated to each other through a divalent metal ion. A crystal structure of an MTM analogue, MTM SA-Phe, in the active metal ion-coordinated dimeric form demonstrates how the stereochemical features of MTM define the helicity of the dimeric scaffold for its binding to a right-handed DNA double helix. We also show crystallographically and biochemically that MTM, but not MTM SA-Phe, can be inactivated by boric Acid through formation of a large macrocyclic species, in which two molecules of MTM are crosslinked to each other through 3-side chain–boron–sugar intermolecular bonds. We discuss these structural and biochemical properties in the context of MTM biosynthesis and the design of MTM analogues as anticancer therapeutics.
-
investigating mithramycin deoxysugar biosynthesis enzymatic total synthesis of tdp d olivose
ChemBioChem, 2011Co-Authors: Guojun Wang, Pallab Pahari, Madan K Kharel, Jurgen RohrAbstract:Natural products often possess one or more highly modified deoxysugar moieties, which are generally critical for their biological activities.[1-3] Mithramycin (MTM), an Aureolic Acid-type anticancer agent, contains five deoxyhexoses, a trisaccharidal chain (d-olivosyl-3-1-d-oliosyl-3-1-d-mycarosyl) and a disaccharidal chain (d-olivosyl-3-1-d-olivosyl) attached at 2- and 6-positions of the aglycon, respectively.[4,5] Among all sugars, d-olivose is the main building component (sugars A, B and C in Scheme 1). In addition to MTM, d-olivose is also an essential component of many biologically active natural products, including all other Aureolic Acid-family anticancer agents and many angucyclines.[5-8] Recently, increasing effort has been made to alter the deoxysugar moiety of natural products (glycodiversification), as modifications to these important structural motifs can greatly influence their activity and substrate specificity.[3,9-14] This approach requires a thorough understanding of deoxysugar biosynthesis as well as suitable glycosyltransferases (GTs), a group of enzymes able to transfer sugars to a given acceptor substrate.[15-17] However, most deoxysugar biosynthesis and glycosylation events, including those involved in MTM biosynthesis, have not been fully characterized in vitro due to the unavailability of sugar donor substrates and soluble glycosyltransferases.[2,9,18] In the MTM pathway, genes involved in the biosynthesis and attachment of deoxysugars have largely been investigated by in vivo studies.[5,19-23] The presence of five sugar moieties but only four GTs indicated that the MTM pathway does not follow the typical “one GT one glycosylation event” rule. Specifically, a unique GT MtmGIV has been suggested to be responsible for the first and third glycosylation events (attaching sugars C and E, respectively), whereas sugars D, A and B are transferred by MtmGIII, MtmGI and MtmGII, respectively.[22-24] Here, we report an in vitro large-scale preparation of thymidine diphosphate (TDP)-d-olivose based on the investigation of several MTM deoxysugar biosynthetic enzymes.
-
histone deacetylase inhibitors and mithramycin a impact a similar neuroprotective pathway at a crossroad between cancer and neurodegeneration
Pharmaceuticals, 2011Co-Authors: Sama F Sleiman, Jurgen Rohr, Jill Berlin, Manuela Basso, Saravanan S Karuppagounder, Rajiv R. RatanAbstract:Mithramycin A (MTM) and histone deacetylase inhibitors (HDACi) are effective therapeutic agents for cancer and neurodegenerative diseases. MTM is a FDA approved Aureolic Acid-type antibiotic that binds to GC-rich DNA sequences and interferes with Sp1 transcription factor binding to its target sites (GC box). HDACi, on the other hand, modulate the activity of class I and II histone deacetylases. They mediate their protective function, in part, by regulating the acetylation status of histones or transcription factors, including Sp1, and in turn chromatin accessibility to the transcriptional machinery. Because these two classes of structurally and functionally diverse compounds mediate similar therapeutic functions, we investigated whether they act on redundant or synergistic pathways to protect neurons from oxidative death. Non-protective doses of each of the drugs do not synergize to create resistance to oxidative death suggesting that these distinct agents act via a similar pathway. Accordingly, we found that protection by MTM and HDACi is associated with diminished expression of the oncogene, Myc and enhanced expression of a tumor suppressor, p21waf1/cip1. We also find that neuroprotection by MTM or Myc knockdown is associated with downregulation of class I HDAC levels. Our results support a model in which the established antitumor drug MTM or canonical HDACi act via distinct mechanisms to converge on the downregulation of HDAC levels or activity respectively. These findings support the conclusion that an imbalance in histone acetylase and HDAC activity in favor of HDACs is key not only for oncogenic transformation, but also neurodegeneration.
-
www.mdpi.com/journal/pharmaceuticals Article Histone Deacetylase Inhibitors and Mithramycin A Impact a Similar Neuroprotective Pathway at a Crossroad between Cancer and Neurodegeneration
2011Co-Authors: Sama F Sleiman, Jurgen Rohr, Jill Berlin, Manuela Basso, Rajiv R. RatanAbstract:Abstract: Mithramycin A (MTM) and histone deacetylase inhibitors (HDACi) are effective therapeutic agents for cancer and neurodegenerative diseases. MTM is a FDA approved Aureolic Acid-type antibiotic that binds to GC-rich DNA sequences and interferes with Sp1 transcription factor binding to its target sites (GC box). HDACi, on the other hand, modulate the activity of class I and II histone deacetylases. They mediate their protective function, in part, by regulating the acetylation status of histones or transcription factors, including Sp1, and in turn chromatin accessibility to the transcriptional machinery. Because these two classes of structurally and functionally diverse compounds mediate similar therapeutic functions, we investigated whether they act on redundant or synergistic pathways to protect neurons from oxidative death. Non-protective doses of each of the drugs do not synergize to create resistance to oxidative death suggesting that these distinct agents act via a similar pathway. Accordingly, we found that protection by MTM and HDACi is associated with diminished expression of the oncogene, Myc and enhance
-
inhibition of sp1 dependent transcription and antitumor activity of the new Aureolic Acid analogues mithramycin sdk and sk in human ovarian cancer xenografts
Gynecologic Oncology, 2010Co-Authors: Sara Previdi, Jurgen Rohr, Giuseppina M Carbone, Veronica Albertini, Anastasia Malek, Cristina Riva, Carlo Capella, Massimo Broggini, Carlo V CatapanoAbstract:Abstract Objective Increased activity of Sp family of transcription factors is a frequent and critical event in cancer development and progression. Genes governing tumor growth, invasion and angiogenesis are regulated by Sp factors, like Sp1, Sp3 or Sp4, and are frequently over-expressed in tumors. Targeting Sp factors has been explored as a therapeutic approach. Mithramycin (MTM) is a natural antibiotic that binds DNA and inhibit Sp1-dependent transcription. New analogues, named MTM-SDK and MTM-SK, were recently obtained by genetic engineering of the MTM biosynthetic pathway and have demonstrated improved transcriptional and antiproliferative activity in ovarian cancer cell lines in vitro . In the present study we evaluated the activity of the new compounds in human ovarian cancer xenografts. Methods Expression of Sp1 and target proteins in ovarian cancer specimens and tumor xenografts was assessed by immunohistochemistry. Drug-induced silencing of Sp1-regulated genes in cells and tumor xenograft samples was assessed by quantitative RT-PCR. Toxicity and antitumor activity of the compounds were investigated in healthy and tumor-bearing immunocompromised mice, respectively. Results Expression of Sp1 was frequently increased in human epithelial ovarian cancers. MTM-SDK and MTM-SK acted as potent inhibitors of Sp1-dependent transcription both in vitro and in tumor xenografts. Both compounds were well tolerated even after prolonged administration and delayed growth of ovarian tumor xenografts. MTM-SDK was particularly effective against orthotopic tumors leading to a significant increase of survival and delay of tumor progression. Conclusions MTM-SDK and MTM-SK show relevant activity in vivo and represent interesting candidates for treatment of ovarian cancers.
Dipak Dasgupta - One of the best experts on this subject based on the ideXlab platform.
-
self association of the anionic form of the dna binding anticancer drug mithramycin
Journal of Physical Chemistry B, 2008Co-Authors: Shibojyoti Lahiri, Pukhrambam Grihanjali Devi, Parijat Majumder, Dipak DasguptaAbstract:The aqueous-phase self-association of mithramycin (MTR), an Aureolic Acid anticancer antibiotic, has been studied using different spectroscopic techniques such as absorption, fluorescence, circular dichroism, and 1H nuclear magnetic resonance spectroscopy. Results from these studies indicate self-association of the anionic antibiotic at pH 8.0 over a concentration range from micromolar to millimolar. These results could be ascribed to the following steps of self-association: M + M ⇆ M2, M2 + M ⇆ M3, and M3 + M ⇆ M4, where M, M2, M3, and M4 represent the monomer, dimer, trimer, and tetramer of mithramycin, respectively. Dynamic light scattering and isothermal titration calorimetry studies also support aggregation. In contrast, an insignificant extent of self-association is found for the neutral drug (at pH 3.5) and the [(MTR)2Mg2+] complex (at pH 8.0). Analysis of 2D NMR spectra of 1 mM MTR suggests that the sugar moieties play a role in the self-association process. Self-association of the drug might occu...
-
self association of the anionic form of the dna binding anticancer drug mithramycin
Journal of Physical Chemistry B, 2008Co-Authors: Shibojyoti Lahiri, Pukhrambam Grihanjali Devi, Parijat Majumder, Suman Das, Dipak DasguptaAbstract:The aqueous-phase self-association of mithramycin (MTR), an Aureolic Acid anticancer antibiotic, has been studied using different spectroscopic techniques such as absorption, fluorescence, circular dichroism, and 1H nuclear magnetic resonance spectroscopy. Results from these studies indicate self-association of the anionic antibiotic at pH 8.0 over a concentration range from micromolar to millimolar. These results could be ascribed to the following steps of self-association: M + M left arrow over right arrow M2, M2 + M left arrow over right arrow M3, and M3 + M left arrow over right arrow M4, where M, M2, M3, and M4 represent the monomer, dimer, trimer, and tetramer of mithramycin, respectively. Dynamic light scattering and isothermal titration calorimetry studies also support aggregation. In contrast, an insignificant extent of self-association is found for the neutral drug (at pH 3.5) and the [(MTR)2Mg2+] complex (at pH 8.0). Analysis of 2D NMR spectra of 1 mM MTR suggests that the sugar moieties play a role in the self-association process. Self-association of the drug might occur either via hydrophobic interaction of the sugar residues among themselves or water-mediated hydrogen bond formation between sugar residue(s). On the other hand, absence of a significant upfield shift of the aromatic protons from 100 microM to 1 mM MTR suggests against the possibility of stacking interactions between the aromatic rings as a stabilizing force for the formation of the dimer and higher oligomers.
-
association of antitumor antibiotics mithramycin and chromomycin with zn ii
Journal of Inorganic Biochemistry, 2007Co-Authors: Pukhrambam Grihanjali Devi, Sudipta Pal, Raja Banerjee, Dipak DasguptaAbstract:Abstract Chromomycin A 3 (CHR) and mithramycin (MTR), members of the Aureolic Acid anticancer antibiotics, supposedly act by inhibiting transcription via reversible association with DNA. The complex(es) with bivalent cation such as Mg 2+ and Zn 2+ is (are) the DNA-binding ligand(s). In this paper, we report a detailed study of the association of these antibiotics with the biologically important bivalent cation, Zn 2+ , because the zinc chelating ability of the antibiotics has therapeutic potential in the treatment of diseases relating to zinc dyshomeostasis. Spectroscopic methods such as absorbance, fluorescence, and circular dichroism and NMR spectroscopy have been used to characterize and understand the mechanism of complex formation. Our data show that both antibiotics form a single complex with Zn 2+ in the mole ratio of 2:1 in terms of antibiotic:Zn 2+ with an apparent binding affinity in the micro molar range. The complex has been characterized as [( D ) 2 Zn 2+ ] (where ‘ D ’ stands for the antibiotic). The kinetics study of the complex formation between the antibiotic(s) and Zn 2+ suggests the following mechanism: D + Zn 2 + ⇆ k - 1 k 1 fast ( D ) Zn 2 + → k 2 slow ( D ) Zn 2 + * → + D fast [ ( D ) 2 Zn 2 + ] Isothermal calorimetric titration has shown that the association is entropy driven, implying the role of water molecules in complex formation. 1 H NMR spectroscopic data of the complex favor a tetrahedral arrangement around the Zn 2+ ion with the antibiotic acting as a bidentate ligand.
Rajiv R. Ratan - One of the best experts on this subject based on the ideXlab platform.
-
histone deacetylase inhibitors and mithramycin a impact a similar neuroprotective pathway at a crossroad between cancer and neurodegeneration
Pharmaceuticals, 2011Co-Authors: Sama F Sleiman, Jurgen Rohr, Jill Berlin, Manuela Basso, Saravanan S Karuppagounder, Rajiv R. RatanAbstract:Mithramycin A (MTM) and histone deacetylase inhibitors (HDACi) are effective therapeutic agents for cancer and neurodegenerative diseases. MTM is a FDA approved Aureolic Acid-type antibiotic that binds to GC-rich DNA sequences and interferes with Sp1 transcription factor binding to its target sites (GC box). HDACi, on the other hand, modulate the activity of class I and II histone deacetylases. They mediate their protective function, in part, by regulating the acetylation status of histones or transcription factors, including Sp1, and in turn chromatin accessibility to the transcriptional machinery. Because these two classes of structurally and functionally diverse compounds mediate similar therapeutic functions, we investigated whether they act on redundant or synergistic pathways to protect neurons from oxidative death. Non-protective doses of each of the drugs do not synergize to create resistance to oxidative death suggesting that these distinct agents act via a similar pathway. Accordingly, we found that protection by MTM and HDACi is associated with diminished expression of the oncogene, Myc and enhanced expression of a tumor suppressor, p21waf1/cip1. We also find that neuroprotection by MTM or Myc knockdown is associated with downregulation of class I HDAC levels. Our results support a model in which the established antitumor drug MTM or canonical HDACi act via distinct mechanisms to converge on the downregulation of HDAC levels or activity respectively. These findings support the conclusion that an imbalance in histone acetylase and HDAC activity in favor of HDACs is key not only for oncogenic transformation, but also neurodegeneration.
-
www.mdpi.com/journal/pharmaceuticals Article Histone Deacetylase Inhibitors and Mithramycin A Impact a Similar Neuroprotective Pathway at a Crossroad between Cancer and Neurodegeneration
2011Co-Authors: Sama F Sleiman, Jurgen Rohr, Jill Berlin, Manuela Basso, Rajiv R. RatanAbstract:Abstract: Mithramycin A (MTM) and histone deacetylase inhibitors (HDACi) are effective therapeutic agents for cancer and neurodegenerative diseases. MTM is a FDA approved Aureolic Acid-type antibiotic that binds to GC-rich DNA sequences and interferes with Sp1 transcription factor binding to its target sites (GC box). HDACi, on the other hand, modulate the activity of class I and II histone deacetylases. They mediate their protective function, in part, by regulating the acetylation status of histones or transcription factors, including Sp1, and in turn chromatin accessibility to the transcriptional machinery. Because these two classes of structurally and functionally diverse compounds mediate similar therapeutic functions, we investigated whether they act on redundant or synergistic pathways to protect neurons from oxidative death. Non-protective doses of each of the drugs do not synergize to create resistance to oxidative death suggesting that these distinct agents act via a similar pathway. Accordingly, we found that protection by MTM and HDACi is associated with diminished expression of the oncogene, Myc and enhance
-
sequence selective dna binding drugs mithramycin a and chromomycin a3 are potent inhibitors of neuronal apoptosis induced by oxidative stress and dna damage in cortical neurons
Annals of Neurology, 2001Co-Authors: Sukalyan Chatterjee, Khalequz Zaman, Hoon Ryu, Adriana Bastos Conforto, Rajiv R. RatanAbstract:Global inhibitors of RNA or protein synthesis such as actinomycin D or cycloheximide abrogate neuronal apoptosis induced by numerous pathological stimuli in vitro and in vivo. The clinical application of actinomycin D or cycloheximide to human neurological disease has been limited by the toxicities of these agents. To overcome these toxicities, strategies must be developed to inhibit selectively the expression of deleterious proapoptotic proteins, while leaving the expression of antiapoptotic, proregeneration, and other critical homeostatic proteins unperturbed. Mithramycin A (trade name Plicamycin) is an Aureolic Acid antibiotic that has been used in humans to treat hypercalcemia and several types of cancers. This class of agents is believed to act, in part, by selectively inhibiting gene expression by displacing transcriptional activators that bind to G-C-rich regions of promoters. Here we demonstrate that mithramycin A and its structural analog chromomycin A3 are potent inhibitors of neuronal apoptosis induced by glutathione depletion-induced oxidative stress or the DNA-damaging agent camptothecin. We correlate the protective effects of mithramycin A with its ability to inhibit enhanced DNA binding of the transcription factors Sp1 and Sp3 to their cognate "G-C" box induced by oxidative stress or DNA damage. The protective effects of mithramycin A cannot be attributed to global inhibition of protein synthesis. Together, these results suggest that mithramycin A and its structural analogs may be effective agents for the treatment of neurological diseases associated with aberrant activation of apoptosis and highlight the potential use of sequence-selective DNA-binding drugs as neurological therapeutics.
Carmen Mendez - One of the best experts on this subject based on the ideXlab platform.
-
lipase catalyzed preparation of chromomycin a3 analogues and biological evaluation for anticancer activity
Bioorganic & Medicinal Chemistry Letters, 2012Co-Authors: Javier Gonzalezsabin, Alejandro F. Braña, Nuria Menendez, Carmen Mendez, Luz Elena Nunez, Jose A Salas, Vicente Gotor, Francisco MorisAbstract:Abstract Several acyl derivatives of the Aureolic Acid chromomycin A 3 were obtained via lipase-catalyzed acylation. Lipase B from Candida antarctica (CAL-B) was found to be the only active biocatalyst, directing the acylation regioselectively towards the terminal secondary hydroxyl group of the aglycone side chain. All new chromomycin A 3 derivatives showed antitumor activity at the micromolar or lower level concentration. Particularly, chromomycin A 3 4′-vinyladipate showed 3–5 times higher activity against the four tumor cell lines assayed as compared to chromomycin A 3 .
-
tailoring modification of deoxysugars during biosynthesis of the antitumour drug chromomycin a3 by streptomyces griseus ssp griseus
Molecular Microbiology, 2004Co-Authors: Nuria Menendez, Jurgen Rohr, Alejandro F. Braña, Mohammad Nurealam, Jose A Salas, Carmen MendezAbstract:Chromomycin A 3 is a member of the Aureolic Acid group family of antitumour drugs.Three tailoring modification steps occur during its biosynthesis affecting the sugar moieties: two O-acetylations and one O-methylation. The 4-O-methylation in the 4-O-methyl-D-oliose moiety of the disaccharide chain is catalysed by the cmmMIII gene product. Inactivation of this gene generated a chromomycin-non-producing mutant that accumulated three unmethylated derivatives containing all sugars but differing in the acylation pattern. Two of these compounds were shown to be substrates of the methyltransferase as determined by their bioconversion into chromomycin A 2 and A 3 after feeding these compounds to a Streptomyces albus strain expressing the cmmMIII gene. The same single membrane-bound enzyme, encoded by the cmmA gene, is responsible for both acetyl transfer reactions, which convert a relatively inactive compound into the bioactive chromomycin A 3 . Insertional inactivation of this gene resulted in a mutant accumulating a dide-acetylated chromomycin A 3 derivative. This compound, lacking both acetyl groups, was converted in a two-step reaction via the 4E-monoacetylated intermediate into chromomycin A 3 when fed to cultures of S. albus expressing the cmmA gene. This acetylation step would occur as the last step in chromomycin biosynthesis, being a very important event for self-protection of the producing organism. It would convert a molecule with low biological activity into an active one, in a reaction catalysed by an enzyme that is predicted to be located in the cell membrane.
-
the structures of premithramycinone and demethylpremithramycinone plausible early intermediates of the Aureolic Acid group antibiotic mithramycin
Chemical Communications, 1998Co-Authors: Jurgen Rohr, Alejandro F. Braña, Eva Künzel, Laura Prado, Ulrike Weisbach, Claus Beninga, Karsten Siems, Kai U Bindseil, Felipe Lombo, Carmen MendezAbstract:The structures of premithramycinone and its demethyl analogue suggest that the Aureolic Acid antibiotics are biosynthetically formed via a tetracycline-type, and not a tetracenomycin-type, folded decaketide.
Alejandro F. Braña - One of the best experts on this subject based on the ideXlab platform.
-
lipase catalyzed preparation of chromomycin a3 analogues and biological evaluation for anticancer activity
Bioorganic & Medicinal Chemistry Letters, 2012Co-Authors: Javier Gonzalezsabin, Alejandro F. Braña, Nuria Menendez, Carmen Mendez, Luz Elena Nunez, Jose A Salas, Vicente Gotor, Francisco MorisAbstract:Abstract Several acyl derivatives of the Aureolic Acid chromomycin A 3 were obtained via lipase-catalyzed acylation. Lipase B from Candida antarctica (CAL-B) was found to be the only active biocatalyst, directing the acylation regioselectively towards the terminal secondary hydroxyl group of the aglycone side chain. All new chromomycin A 3 derivatives showed antitumor activity at the micromolar or lower level concentration. Particularly, chromomycin A 3 4′-vinyladipate showed 3–5 times higher activity against the four tumor cell lines assayed as compared to chromomycin A 3 .
-
tailoring modification of deoxysugars during biosynthesis of the antitumour drug chromomycin a3 by streptomyces griseus ssp griseus
Molecular Microbiology, 2004Co-Authors: Nuria Menendez, Jurgen Rohr, Alejandro F. Braña, Mohammad Nurealam, Jose A Salas, Carmen MendezAbstract:Chromomycin A 3 is a member of the Aureolic Acid group family of antitumour drugs.Three tailoring modification steps occur during its biosynthesis affecting the sugar moieties: two O-acetylations and one O-methylation. The 4-O-methylation in the 4-O-methyl-D-oliose moiety of the disaccharide chain is catalysed by the cmmMIII gene product. Inactivation of this gene generated a chromomycin-non-producing mutant that accumulated three unmethylated derivatives containing all sugars but differing in the acylation pattern. Two of these compounds were shown to be substrates of the methyltransferase as determined by their bioconversion into chromomycin A 2 and A 3 after feeding these compounds to a Streptomyces albus strain expressing the cmmMIII gene. The same single membrane-bound enzyme, encoded by the cmmA gene, is responsible for both acetyl transfer reactions, which convert a relatively inactive compound into the bioactive chromomycin A 3 . Insertional inactivation of this gene resulted in a mutant accumulating a dide-acetylated chromomycin A 3 derivative. This compound, lacking both acetyl groups, was converted in a two-step reaction via the 4E-monoacetylated intermediate into chromomycin A 3 when fed to cultures of S. albus expressing the cmmA gene. This acetylation step would occur as the last step in chromomycin biosynthesis, being a very important event for self-protection of the producing organism. It would convert a molecule with low biological activity into an active one, in a reaction catalysed by an enzyme that is predicted to be located in the cell membrane.
-
biosynthesis of the antitumor chromomycin a3 in streptomyces griseus analysis of the gene cluster and rational design of novel chromomycin analogs
Chemistry & Biology, 2004Co-Authors: Nuria Menendez, Alejandro F. Braña, Mohammad Nurealam, Jurgen RohrAbstract:Abstract The biosynthetic gene cluster of the Aureolic Acid type antitumor drug chromomycin A 3 from S. griseus subsp. griseus has been identified and characterized. It spans 43 kb and contains 36 genes involved in polyketide biosynthesis and modification, deoxysugar biosynthesis and sugar transfer, pathway regulation and resistance. The organization of the cluster clearly differs from that of the closely related mithramycin. Involvement of the cluster in chromomycin A 3 biosynthesis was demonstrated by disrupting the cmmWI gene encoding a polyketide reductase involved in side chain reduction. Three novel chromomycin derivatives were obtained, named chromomycin SK, chromomycin SA, and chromomycin SDK, which show antitumor activity and differ with respect to their 3-side chains. A pathway for the biosynthesis of chromomycin A 3 and its deoxysugars is proposed.
-
the structures of premithramycinone and demethylpremithramycinone plausible early intermediates of the Aureolic Acid group antibiotic mithramycin
Chemical Communications, 1998Co-Authors: Jurgen Rohr, Alejandro F. Braña, Eva Künzel, Laura Prado, Ulrike Weisbach, Claus Beninga, Karsten Siems, Kai U Bindseil, Felipe Lombo, Carmen MendezAbstract:The structures of premithramycinone and its demethyl analogue suggest that the Aureolic Acid antibiotics are biosynthetically formed via a tetracycline-type, and not a tetracenomycin-type, folded decaketide.
