Dynemicin A
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| Category | New Products |
| Catalog number | BBF-01775 |
| CAS | 124412-57-3 |
| Molecular Weight | 537.47 |
| Molecular Formula | C30H19NO9 |
| Purity | 95% |
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Description
It is produced by the strain of Micromonospora chersina sp. M 956-I and M. globosa. Dynemicin A has a strong killing effect on a variety of tumor cells at Pg/mL level. The cyclic enediyne part of enediyne antibiotics is cycled by Bergman to form aromatic diradicals, which quickly seize hydrogen atoms from the DNA skeleton and break the DNA strand, thus killing tumor cells.
Specification
| Related CAS | 124759-75-7 |
| Synonyms | (1S,4R,4aR,14S,14aS)-1,4,4a,7,12,13,14,14a-Octahydro-6,8,11-trihydroxy-3-methoxy-1-methyl-7,12-dioxo-4a,14a-epoxy-4,14-(3-hexene-1,5-diyne-1,6-diyl)naphtho[2,3-c]phenanthridine-2-carboxylicacid; Dynemicin; BU 3420T |
| IUPAC Name | (2R,4S,5S,8R,11Z,15S)-21,24,28-trihydroxy-7-methoxy-5-methyl-19,26-dioxo-3-oxa-16-azaheptacyclo[15.12.0.02,4.02,8.04,15.018,27.020,25]nonacosa-1(29),6,11,17,20,22,24,27-octaen-9,13-diyne-6-carboxylic acid |
| Canonical SMILES | CC1C(=C(C2C#CC=CC#CC3C14C2(O4)C5=CC(=C6C(=C5N3)C(=O)C7=C(C=CC(=C7C6=O)O)O)O)OC)C(=O)O |
| InChI | InChI=1S/C30H19NO9/c1-12-19(28(37)38)27(39-2)13-7-5-3-4-6-8-18-29(12)30(13,40-29)14-11-17(34)22-23(24(14)31-18)26(36)21-16(33)10-9-15(32)20(21)25(22)35/h3-4,9-13,18,31-34H,1-2H3,(H,37,38)/b4-3-/t12-,13+,18-,29-,30+/m0/s1 |
| InChI Key | AFMYMMXSQGUCBK-AKMKHHNQSA-N |
Properties
| Appearance | Purple Amorphous Powder |
| Antibiotic Activity Spectrum | Neoplastics (Tumor) |
| Melting Point | 208-210 °C |
| Solubility | Soluble in DMSO, DMF, Dioxane; Fairly soluble in Methanol, Ethanol, Isopropanol, Ethyl Acetate; Insoluble in Water, Hexane |
Reference Reading
1.Docking, triggering, and biological activity of dynemicin A in DNA: a computational study.
Tuttle T1, Kraka E, Cremer D. J Am Chem Soc. 2005 Jul 6;127(26):9469-84.
The triggering and biological activity of the naturally occurring enediyne dynemicin A (1) was investigated, both inside and outside the minor groove of the duplex 10-mer B-DNA sequence d(CTACTACTGG).d(CCAGTAGTAG), using density functional theory (B3LYP with the 3-21G and 6-31G(d) basis set), BD(T)/cc-pVDZ (Brueckner doubles with a perturbative treatment of triple excitations), and the ONIOM approach. Enediyne 1 is triggered by NADPH in a strongly exothermic reaction (-88 kcal/mol), which involves a number of intermediate steps. Untriggered 1 has a high barrier for the Bergman cyclization (52 kcal/mol) that is lowered after triggering to 16.7 kcal/mol due to an epoxide opening and the accompanying strain relief. The Bergman reaction of triggered 1 is slightly exothermic by 2.8 kcal/mol. The singlet biradical formed in this reaction is kinetically stable (activation enthalpies of 19.5 and 21.8 kcal/mol for retro-Bergman reactions) and is as reactive as para-benzyne.
2.A QM/MM study of the Bergman reaction of dynemicin A in the minor groove of DNA.
Tuttle T1, Kraka E, Thiel W, Cremer D. J Phys Chem B. 2007 Jul 19;111(28):8321-8. Epub 2007 Jun 22.
The Bergman cyclization of the natural enediyne dynemicin A in its triggered form (2) bound to the minor groove of DNA is compared with the corresponding reaction of its open isomer (4) utilizing QM/MM methodology. The two isomers are typical representatives of 10-membered cyclic (2) and acyclic (4) enediynes, which possess significantly different barriers for the Bergman reaction in the gas phase (2, 20.4 kcal/mol; 4, 31.3 kcal/mol). In the case of the cyclic enediyne (2) the explicit consideration of environmental factors such as the receptor DNA, the solvent water, and charge neutralization by counterions has only minor effects on the energy profile of the cyclization reaction and the corresponding optimized structures when compared with the gas phase. The energetics of the reaction is predominantly determined by QM (electronic) effects. This makes it possible to replace the explicit description of the environment by an implicit one, thus avoiding costly QM/MM calculations and using instead a decoupled QM+MM approach.
3.Prodrugs of dynemicin analogs for selective chemotherapy mediated by an aldolase catalytic Ab.
Sinha SC1, Li LS, Miller GP, Dutta S, Rader C, Lerner RA. Proc Natl Acad Sci U S A. 2004 Mar 2;101(9):3095-9. Epub 2004 Feb 23.
Prodrugs of dynemicin analogs were synthesized, and their activation by aldolase antibody (Ab) 38C2 was evaluated by DNA-cleaving activity, as well as tumor cell growth inhibition. Further, we provide evidence that the activated enediynes underwent covalent crosscoupling with the aldolase Ab, which appears to be a limiting factor of their tumor cell growth-inhibiting activity and should be of general interest in the field of enediyne chemotherapy. These findings might open new avenues for defined conjugations of small molecule drugs to mAbs in general and aldolase Abs in particular.
4.Induced-fit upon ligand binding revealed by crystal structures of the hot-dog fold thioesterase in dynemicin biosynthesis.
Liew CW1, Sharff A, Kotaka M, Kong R, Sun H, Qureshi I, Bricogne G, Liang ZX, Lescar J. J Mol Biol. 2010 Nov 26;404(2):291-306. doi: 10.1016/j.jmb.2010.09.041. Epub 2010 Oct 1.
Dynemicins are structurally related 10-membered enediyne natural products isolated from Micromonospora chernisa with potent antitumor and antibiotic activity. The early biosynthetic steps of the enediyne moiety of dynemicins are catalyzed by an iterative polyketide synthase (DynE8) and a thioesterase (DynE7). Recent studies indicate that the function of DynE7 is to off-load the linear biosynthetic intermediate assembled on DynE8. Here, we report crystal structures of DynE7 in its free form at 2.7 Å resolution and of DynE7 in complex with the DynE8-produced all-trans pentadecen-2-one at 2.1 Å resolution. These crystal structures reveal that upon ligand binding, significant conformational changes throughout the substrate-binding tunnel result in an expanded tunnel that traverses an entire monomer of the tetrameric DynE7 protein. The enlarged inner segment of the channel binds the carbonyl-conjugated polyene mainly through hydrophobic interactions, whereas the putative catalytic residues are located in the outer segment of the channel.
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Bio Calculators
* Our calculator is based on the following equation:
Concentration (start) x Volume (start) = Concentration (final) x Volume (final)
It is commonly abbreviated as: C1V1 = C2V2
* Total Molecular Weight:
g/mol
Tip: Chemical formula is case sensitive. C22H30N4O √ c22h30n40 ╳
