Dynemicin A

Structural formula
General
Surname	Dynemicin A
Molecular formula	C 30 H 19 NO 9
External identifiers / databases
PubChem	10030135
ChemSpider	8205706
Wikidata	Q5319198
properties
Molar mass	537.48 g mol −1
Physical state	firmly
safety instructions
GHS hazard labeling ; no classification available
GHS hazard labeling ; no classification available
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Dynemicin A belongs to the group of angucyclines and enediins .

properties

Dynemicin A reacts via a Bergman cyclization , whereby a para- didehydrobenzene is formed, which induces a double-strand break in B-DNA via its epoxide group . Hence, it is being studied for use as a chemotherapy drug. The strand break occurs randomly with a slight tendency to guanines . The action of Dynemicin A can be inhibited by distamycin A and anthramycin , both of which bind in the minor groove of double-stranded DNA . Therefore, Dynemicin A probably also binds in the minor groove.

synthesis

Dynemicin A biosynthesis

The first total synthesis for Dynemicin A was published in 1995.

Dynemicin A is formed by the actinomycetes Micromonospora chersina (from Gujarat ) and Micromonospora globosa (from Japan ) and was first isolated in the mid-1980s. The biosynthesis takes place via the polyketide route .

Individual evidence

↑ This substance has either not yet been classified with regard to its hazardousness or a reliable and citable source has not yet been found.
^ A. Beane, BR Miller, CA Parish: Internal abstraction of dynemicin A: An MD approach. In: Journal of Molecular Graphics & Modeling . Volume 74, June 2017, pp. 251-264, doi : 10.1016 / j.jmgm.2017.03.012 , PMID 28458004 .
↑ KC Nicolaou, JS Chen, SM Dalby: From nature to the laboratory and into the clinic. In: Bioorganic & Medicinal Chemistry . Volume 17, number 6, March 2009, pp. 2290-2303, doi : 10.1016 / j.bmc.2008.10.089 , PMID 19028103 , PMC 2665039 (free full text).
↑ ^a ^b ^c ^d Daniel Best: Dynemicin A, Uncialamycin and Analogues. Elsevier, 2016, ISBN 978-0-081-01086-0 . P. 1.
^ Andrew G. Myers, Mark E. Fraley, Norma J. Tom, Scott B. Cohen, David J. Madar: Synthesis of (+) - dynemicin A and analogs of wide structural variability: establishment of the absolute configuration of natural dynemicin A. , Chemistry & Biology (1995), 2 (1): pp. 33-43. PMID 9383401 . doi: 10.1016 / 1074-5521 (95) 90078-0 .
↑ Otto D. Hensens, Jose Luis Giner, Irving H. Goldberg: Biosynthesis of NCS Chrom A, the chromophore of the antitumor antibiotic neocarzinostatin , J. Am. Chem. Soc. (1989), 111 (9): pp. 3295-3299. doi: 10.1021 / ja00191a028 .
↑ Yoshiyuki Tokiwa, Megumi Miyoshi-Saitoh, Hisayoshi Kobayashi, Rie Sunaga, Masataka Konishi, Toshikazu Oki, Shigeo Iwasaki: Biosynthesis of dynemicin A, a 3-ene-1,5-diyne antitumor antibiotic , J. Am. Chem. Soc. (1992), 114 (11): pp. 4107-4110. doi: 10.1021 / ja00037a011 .
↑ Wen Liu, Joachim Ahlert, Qunjie Gao, Evelyn Wendt-Pienkowski, Ben Shen, Jon S. Thorson: Rapid PCR amplification of minimal enediyne polyketide synthase cassettes leads to a predictive familial classification model , Proceedings of the National Academy of Sciences of the United States of America (2003), 100 (21): pp. 11959-11963. PMC 218695 (free full text). PMID 14528002 . doi: 10.1073 / pnas.2034291100 .
↑ Qunjie Gao, Jon S. Thorson: The biosynthetic genes encoding for the production of the dynemicin enediyne core in Micromonospora chersina ATCC53710 , FEMS Microbiology Letters (2008), 282 (1): pp. 105-114. PMID 18328078 . doi: 10.1111 / j.1574-6968.2008.01112.x .

[NV-1] This substance has either not yet been classified with regard to its hazardousness or a reliable and citable source has not yet been found.

[2] A. Beane, BR Miller, CA Parish: Internal abstraction of dynemicin A: An MD approach. In: Journal of Molecular Graphics & Modeling . Volume 74, June 2017, pp. 251-264, doi : 10.1016 / j.jmgm.2017.03.012 , PMID 28458004 .

[3] KC Nicolaou, JS Chen, SM Dalby: From nature to the laboratory and into the clinic. In: Bioorganic & Medicinal Chemistry . Volume 17, number 6, March 2009, pp. 2290-2303, doi : 10.1016 / j.bmc.2008.10.089 , PMID 19028103 , PMC 2665039 (free full text).

[Best-4] Daniel Best: Dynemicin A, Uncialamycin and Analogues. Elsevier, 2016, ISBN 978-0-081-01086-0 . P. 1.

[5] Andrew G. Myers, Mark E. Fraley, Norma J. Tom, Scott B. Cohen, David J. Madar: Synthesis of (+) - dynemicin A and analogs of wide structural variability: establishment of the absolute configuration of natural dynemicin A. , Chemistry & Biology (1995), 2 (1): pp. 33-43. PMID 9383401 . doi: 10.1016 / 1074-5521 (95) 90078-0 .

[6] Otto D. Hensens, Jose Luis Giner, Irving H. Goldberg: Biosynthesis of NCS Chrom A, the chromophore of the antitumor antibiotic neocarzinostatin , J. Am. Chem. Soc. (1989), 111 (9): pp. 3295-3299. doi: 10.1021 / ja00191a028 .

[7] Yoshiyuki Tokiwa, Megumi Miyoshi-Saitoh, Hisayoshi Kobayashi, Rie Sunaga, Masataka Konishi, Toshikazu Oki, Shigeo Iwasaki: Biosynthesis of dynemicin A, a 3-ene-1,5-diyne antitumor antibiotic , J. Am. Chem. Soc. (1992), 114 (11): pp. 4107-4110. doi: 10.1021 / ja00037a011 .

[8] Wen Liu, Joachim Ahlert, Qunjie Gao, Evelyn Wendt-Pienkowski, Ben Shen, Jon S. Thorson: Rapid PCR amplification of minimal enediyne polyketide synthase cassettes leads to a predictive familial classification model , Proceedings of the National Academy of Sciences of the United States of America (2003), 100 (21): pp. 11959-11963. PMC 218695 (free full text). PMID 14528002 . doi: 10.1073 / pnas.2034291100 .

[9] Qunjie Gao, Jon S. Thorson: The biosynthetic genes encoding for the production of the dynemicin enediyne core in Micromonospora chersina ATCC53710 , FEMS Microbiology Letters (2008), 282 (1): pp. 105-114. PMID 18328078 . doi: 10.1111 / j.1574-6968.2008.01112.x .