Tomaymycin
* Please be kindly noted products are not for therapeutic use. We do not sell to patients.
| Category | Antibiotics |
| Catalog number | BBF-03420 |
| CAS | 35050-55-6 |
| Molecular Weight | 304.34 |
| Molecular Formula | C16H20N2O4 |
Online Inquiry
Description
It is originally isolated from Str. achromogenes var. tomaymyceticus A-2127. Tomaymycin is resistant to gram-positive bacteria and fungi, and has a weak effect on E. coli.
Specification
| Synonyms | NSC 177499; 2-Ethylidene-1,2,3,10,11,11a-hexahydro-8-hydroxy-7,11-dimethoxy-5H-pyrrolo(2,1-c)(1,4)benzodiazepin-5-one |
| IUPAC Name | (6R,6aS,8E)-8-ethylidene-3-hydroxy-2,6-dimethoxy-6,6a,7,9-tetrahydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-11-one |
| Canonical SMILES | CC=C1CC2C(NC3=CC(=C(C=C3C(=O)N2C1)OC)O)OC |
| InChI | InChI=1S/C16H20N2O4/c1-4-9-5-12-15(22-3)17-11-7-13(19)14(21-2)6-10(11)16(20)18(12)8-9/h4,6-7,12,15,17,19H,5,8H2,1-3H3/b9-4+/t12-,15+/m0/s1 |
| InChI Key | UQVNRKBFAXNOGA-LWTNMJDUSA-N |
Properties
| Appearance | Colorless Flaky Crystal |
| Antibiotic Activity Spectrum | Gram-positive bacteria; fungi |
| Boiling Point | 445.17°C at 760 mmHg |
| Melting Point | 145-146°C |
| Density | 1.1328 g/cm3 |
Reference Reading
1. One- and two-dimensional 1H NMR, fluorescence, and molecular modeling studies on the tomaymycin-d(ATGCAT)2 adduct. Evidence for two covalent adducts with opposite orientations and stereochemistries at the covalent linkage site
W Remers, S Cheatham, A Kook, L H Hurley, M D Barkley J Med Chem . 1988 Mar;31(3):583-90. doi: 10.1021/jm00398a016.
Tomaymycin is a member of the pyrrolo[1,4]benzodiazepine antitumor-antibiotic group that binds covalently to the exocyclic 2-amino group of guanine in DNA. Previous correlation of fluorescence and NMR data suggested that the 11R,11aS and the 11S,11aS diastereomers of tomaymycin could bind to DNA in two orientations relative to the covalently modified guanine (Barkley, M. D.; Cheatham, S.; Thurston, D. E.; Hurley, L. H. Biochemistry 1986, 25, 3021-3031). We now report on fluorescence, one- and two-dimensional proton NMR, and molecular modeling studies of the tomaymycin-d(ATGCAT)2 adduct, which corroborate these earlier observations. Fluorescence measurements show that there are two species of tomaymycin bound to d(ATGCAT)2, which are tentatively identified as the 11R,11aS and 11S,11aS diastereomers. Two distinct sets of signals for the tomaymycin molecule are present in the proton NMR spectrum of the tomaymycin-d(ATGCAT)2 duplex adduct. Two-dimensional correlation spectroscopy (2D-COSY) studies also show connectivities for four cytosine H5-H6 and eight thymine methyl-H6 protons and thus clearly establish the presence of two distinct species of tomaymycin-d(ATGCAT)2 adducts in solution. A single scalar 11-11a 1H NMR coupling in the 2D-COSY spectrum is indicative of an adduct species that has an S configuration at the C-11 position. Two-dimensional nuclear Overhauser effect (NOESY) spectra of the tomaymycin-d(ATGCAT)2 duplex adduct show that the adducts are relatively nondistortive. In a NOESY experiment, cross-peaks were identified between both the aromatic H9 proton and the ethylidine methyl protons of tomaymycin and two different adenine H2 protons of d(ATGCAT)2. Molecular mechanics calculations with AMBER show that the two species with the thermodynamically most favorable binding energies are the 11R,11aS and 11S,11aS isomers with their aromatic rings to the 5' and 3' sides of the covalently bound guanine, respectively. The NOEs observed between tomaymycin protons and adenine H2 protons are in accord with molecular modeling studies. Taken together, these results strongly suggest that the two forms of tomaymycin bound to d(ATGCAT)2 are the 11S,11aS and 11R,11aS species, oriented with their aromatic rings to the 3' and 5' sides, respectively, of the covalently modified guanines.
2. Cloning and characterization of the biosynthetic gene cluster for tomaymycin, an SJG-136 monomeric analog
ShenChieh Chou, Wei Li, Ankush Khullar, Barbara Gerratana Appl Environ Microbiol . 2009 May;75(9):2958-63. doi: 10.1128/AEM.02325-08.
Tomaymycin produced by Streptomyces achromogenes is a naturally produced pyrrolobenzodiazepine (PBD). The biosynthetic gene cluster for tomaymycin was identified and sequenced. The gene cluster analysis reveals a novel biosynthetic pathway for the anthranilate moiety of PBDs. Gene replacement and chemical complementation studies were used to confirm the proposed biosynthetic pathway.
3. Total Biosynthesis of the Pyrrolo[4,2]benzodiazepine Scaffold Tomaymycin on an In Vitro Reconstituted NRPS System
Michael Hoffmann, Alexander von Tesmar, Armin Bauer, Wulf Blankenfeldt, Antoine Abou Fayad, Rolf Müller, Stefan Dausend-Werner, Jan Pippel Cell Chem Biol . 2017 Oct 19;24(10):1216-1227.e8. doi: 10.1016/j.chembiol.2017.08.001.
In vitro reconstitution and biochemical analysis of natural product biosynthetic pathways remains a challenging endeavor, especially if megaenzymes of the nonribosomal peptide synthetase (NRPS) type are involved. In theory, all biosynthetic steps may be deciphered using mass spectrometry (MS)-based analyses of both the carrier protein-coupled intermediates and the free intermediates. We here report the "total biosynthesis" of the pyrrolo[4,2]benzodiazepine scaffold tomaymycin using an in vitro reconstituted NRPS system. Proteoforms were analyzed by liquid chromatography (LC)-MS to decipher every step of the biosynthesis on its respective megasynthetase with up to 170 kDa in size. To the best of our knowledge, this is the first report of a comprehensive analysis of virtually all chemical steps involved in the biosynthesis of nonribosomally synthesized natural products. The study includes experiments to determine substrate specificities of the corresponding A-domains in competition assays by analyzing the adenylation step as well as the transfer to the respective carrier protein domain.
Recommended Products
| BBF-01825 | Loganin | Inquiry |
| BBF-01829 | Deoxynojirimycin | Inquiry |
| BBF-02614 | Nystatin | Inquiry |
| BBF-05862 | Epirubicin | Inquiry |
| BBF-02642 | Lactonamycin | Inquiry |
| BBF-03754 | CASTANOSPERMINE | Inquiry |
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 ╳
