Indolmycin
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| Category | Antibiotics |
| Catalog number | BBF-01878 |
| CAS | 21200-24-8 |
| Molecular Weight | 257.29 |
| Molecular Formula | C14H15N3O2 |
| Purity | >99% by HPLC (total diastereoisomers) |
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Description
A highly selective antibiotic which acts as a tryptophan anti-metabolite; active against mycobacteria and H. Pylori, and can stimulate transcription in escherichia coli.
Specification
| Synonyms | Indolemycin; PA 155 A; (-)-indolmycin; (1R,5S)-(-)-5-(1-Indol-3-ylethyl)-2-(methylamino)-2-oxazolin-4-one |
| Storage | -20°C |
| IUPAC Name | (5S)-5-[(1R)-1-(1H-indol-3-yl)ethyl]-2-methylimino-1,3-oxazolidin-4-one |
| Canonical SMILES | CC(C1C(=O)NC(=NC)O1)C2=CNC3=CC=CC=C32 |
| InChI | InChI=1S/C14H15N3O2/c1-8(12-13(18)17-14(15-2)19-12)10-7-16-11-6-4-3-5-9(10)11/h3-8,12,16H,1-2H3,(H,15,17,18)/t8-,12+/m1/s1 |
| InChI Key | GNTVWGDQPXCYBV-PELKAZGASA-N |
| Source | Streptomyces sp. |
Properties
| Appearance | White Powder |
| Antibiotic Activity Spectrum | Gram-positive bacteria; Gram-negative bacteria; mycobacteria |
| Boiling Point | 420.8°C at 760 mmHg |
| Melting Point | 209-210°C |
| Density | 1.36 g/cm3 |
| Solubility | Soluble in ethanol, methanol, DMF or DMSO. Poor water solubility. |
Reference Reading
1. A novel tryptophanyl-tRNA synthetase gene confers high-level resistance to indolmycin
Jason K Sello, James J Vecchione Antimicrob Agents Chemother . 2009 Sep;53(9):3972-80. doi: 10.1128/AAC.00723-09.
Indolmycin, a potential antibacterial drug, competitively inhibits bacterial tryptophanyl-tRNA synthetases. An effort to identify indolmycin resistance genes led to the discovery of a gene encoding an indolmycin-resistant isoform of tryptophanyl-tRNA synthetase. Overexpression of this gene in an indolmycin-sensitive strain increased the indolmycin MIC 60-fold. Its transcription and distribution in various bacterial genera were assessed. The level of resistance conferred by this gene was compared to that of a known indolmycin resistance gene and to those of genes with resistance-conferring point mutations.
2. An engineered biosynthetic-synthetic platform for production of halogenated indolmycin antibiotics
Elesha R Hoffarth, Katherine S Ryan, Sunnie Kong, Hai-Yan He Chem Sci . 2021 Jun 1;12(25):8817-8821. doi: 10.1039/d0sc05843b.
Indolmycin is an antibiotic fromStreptomyces griseusATCC 12648 with activity againstHelicobacter pylori,Plasmodium falciparum, and methicillin-resistantStaphylococcus aureus. Here we describe the use of the indolmycin biosynthetic genes inE. colito make indolmycenic acid, a chiral intermediate in indolmycin biosynthesis, which can then be converted to indolmycin through a three-step synthesis. To expand indolmycin structural diversity, we introduce a promiscuous tryptophanyl-tRNA synthetase gene (trpS) into ourE. coliproduction system and feed halogenated indoles to generate the corresponding indolmycenic acids, ultimately allowing us to access indolmycin derivatives through synthesis. Bioactivity testing against methicillin-resistantStaphylococcus aureusshowed modest antibiotic activity for 5-, 6-, and 7-fluoro-indolmycin.
3. Selective Inhibition of Bacterial Tryptophanyl-tRNA Synthetases by Indolmycin Is Mechanism-based
Yuhui W Yin, Tishan L Williams, Charles W Carter Jr J Biol Chem . 2016 Jan 1;291(1):255-65. doi: 10.1074/jbc.M115.690321.
Indolmycin is a natural tryptophan analog that competes with tryptophan for binding to tryptophanyl-tRNA synthetase (TrpRS) enzymes. Bacterial and eukaryotic cytosolic TrpRSs have comparable affinities for tryptophan (Km ~ 2 μm), and yet only bacterial TrpRSs are inhibited by indolmycin. Despite the similarity between these ligands, Bacillus stearothermophilus (Bs)TrpRS preferentially binds indolmycin ~1500-fold more tightly than its tryptophan substrate. Kinetic characterization and crystallographic analysis of BsTrpRS allowed us to probe novel aspects of indolmycin inhibitory action. Previous work had revealed that long range coupling to residues within an allosteric region called the D1 switch of BsTrpRS positions the Mg(2+) ion in a manner that allows it to assist in transition state stabilization. The Mg(2+) ion in the inhibited complex forms significantly closer contacts with non-bridging oxygen atoms from each phosphate group of ATP and three water molecules than occur in the (presumably catalytically competent) pre-transition state (preTS) crystal structures. We propose that this altered coordination stabilizes a ground state Mg(2+)·ATP configuration, accounting for the high affinity inhibition of BsTrpRS by indolmycin. Conversely, both the ATP configuration and Mg(2+) coordination in the human cytosolic (Hc)TrpRS preTS structure differ greatly from the BsTrpRS preTS structure. The effect of these differences is that catalysis occurs via a different transition state stabilization mechanism in HcTrpRS with a yet-to-be determined role for Mg(2+). Modeling indolmycin into the tryptophan binding site points to steric hindrance and an inability to retain the interactions used for tryptophan substrate recognition as causes for the 1000-fold weaker indolmycin affinity to HcTrpRS.
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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 ╳
