GE 2270A
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| Category | Antibiotics |
| Catalog number | BBF-03577 |
| CAS | 134861-34-0 |
| Molecular Weight | 1290.52 |
| Molecular Formula | C56H55N15O10S6 |
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Description
GE 2270A is a thiopeptide antibiotic produced by the strain of Planobispora rosea. It inhibits bacterial protein synthesis and has anti-Gram-positive aerobic and anaerobic bacteria (MIC = 0.03-0.25 μg/mL) and Mycobacterium tuberculosis (MIC = 1 μg/mL) activities.
Specification
| Synonyms | Antibiotic GE 2270A; MDL 62879; Antibiotic MDL 62879; GE-2270A; GE-2270 |
| IUPAC Name | (2S)-1-[(4S)-2-[2-[(18S,25S,35S)-35-[(S)-hydroxy(phenyl)methyl]-28-(methoxymethyl)-21-methyl-18-[2-(methylamino)-2-oxoethyl]-16,23,30,33-tetraoxo-25-propan-2-yl-3,13,20,27,37-pentathia-7,17,24,31,34,39,40,41,42,43-decazaheptacyclo[34.2.1.12,5.112,15.119,22.126,29.06,11]tritetraconta-1(38),2(43),4,6(11),7,9,12(42),14,19(41),21,26(40),28,36(39)-tridecaen-8-yl]-1,3-thiazol-4-yl]-4,5-dihydro-1,3-oxazole-4-carbonyl]pyrrolidine-2-carboxamide |
| Canonical SMILES | CC1=C2C(=O)NC(C3=NC(=C(S3)COC)C(=O)NCC(=O)NC(C4=NC(=CS4)C5=NC(=CS5)C6=C(C=CC(=N6)C7=NC(=CS7)C8=NC(CO8)C(=O)N9CCCC9C(=O)N)C3=NC(=CS3)C(=O)NC(C(=N2)S1)CC(=O)NC)C(C1=CC=CC=C1)O)C(C)C |
| InChI | InChI=1S/C56H55N15O10S6/c1-24(2)39-55-70-42(36(87-55)19-80-5)47(77)59-17-38(73)67-43(44(74)26-10-7-6-8-11-26)54-66-34(23-85-54)52-63-31(20-83-52)41-27(50-64-32(21-82-50)46(76)61-29(16-37(72)58-4)53-69-40(25(3)86-53)48(78)68-39)13-14-28(60-41)51-65-33(22-84-51)49-62-30(18-81-49)56(79)71-15-9-12-35(71)45(57)75/h6-8,10-11,13-14,20-24,29-30,35,39,43-44,74H,9,12,15-19H2,1-5H3,(H2,57,75)(H,58,72)(H,59,77)(H,61,76)(H,67,73)(H,68,78)/t29-,30-,35-,39-,43-,44-/m0/s1 |
| InChI Key | JMDULECOHIXMNX-MZHFYNGJSA-N |
Properties
| Appearance | White Powder |
| Antibiotic Activity Spectrum | Gram-positive bacteria; Mycobacteria |
| Density | 1.7±0.1 g/cm3 |
| Solubility | Soluble in Water |
Reference Reading
1. Antibacterial Thiopeptide GE2270-Congeners from Nonomuraea jiangxiensis
Kuan-Chieh Ching, Elaine J Chin, Mario Wibowo, Zann Y Tan, Lay-Kien Yang, Deborah C Seow, Chung-Yan Leong, Veronica W Ng, Siew-Bee Ng, Yoganathan Kanagasundaram Molecules. 2022 Dec 23;28(1):101. doi: 10.3390/molecules28010101.
Thiopeptides are macrocyclic natural products with potent bioactivity. Nine new natural thiopeptides (1-9) were obtained from a Nonomuraea jiangxiensis isolated from a terrestrial soil sample collected in Singapore. Even though some of these compounds were previously synthesized or isolated from engineered strains, herein we report the unprecedented isolation of these thiopeptides from a native Nonomuraea jiangxiensis. A comparison with the literature and a detailed analysis of the NMR and HRMS of compounds 1-9 was conducted to assign their chemical structures. The structures of all new compounds were highly related to the thiopeptide antibiotics GE2270, with variations in the substituents on the thiazole and amino acid moieties. Thiopeptides 1-9 exhibited a potent antimicrobial activity against the Gram-positive bacteria, Staphylococcus aureus with MIC90 values ranging from 2 µM to 11 µM. In addition, all compounds were investigated for their cytotoxicity against the human cancer cell line A549, none of the compounds were cytotoxic.
2. Structural insights into enzymatic [4+2] aza-cycloaddition in thiopeptide antibiotic biosynthesis
Dillon P Cogan, Graham A Hudson, Zhengan Zhang, Taras V Pogorelov, Wilfred A van der Donk, Douglas A Mitchell, Satish K Nair Proc Natl Acad Sci U S A. 2017 Dec 5;114(49):12928-12933. doi: 10.1073/pnas.1716035114. Epub 2017 Nov 20.
The [4+2] cycloaddition reaction is an enabling transformation in modern synthetic organic chemistry, but there are only limited examples of dedicated natural enzymes that can catalyze this transformation. Thiopeptides (or more formally thiazolyl peptides) are a class of thiazole-containing, highly modified, macrocyclic secondary metabolites made from ribosomally synthesized precursor peptides. The characteristic feature of these natural products is a six-membered nitrogenous heterocycle that is assembled via a formal [4+2] cycloaddition between two dehydroalanine (Dha) residues. This heteroannulation is entirely contingent on enzyme activity, although the mechanism of the requisite pyridine/dehydropiperidine synthase remains to be elucidated. The unusual aza-cylic product is distinct from the more common carbocyclic products of synthetic and biosynthetic [4+2] cycloaddition reactions. To elucidate the mechanism of cycloaddition, we have determined atomic resolution structures of the pyridine synthases involved in the biosynthesis of the thiopeptides thiomuracin (TbtD) and GE2270A (PbtD), in complex with substrates and product analogs. Structure-guided biochemical, mutational, computational, and binding studies elucidate active-site features that explain how orthologs can generate rigid macrocyclic scaffolds of different sizes. Notably, the pyridine synthases show structural similarity to the elimination domain of lanthipeptide dehydratases, wherein insertions of secondary structural elements result in the formation of a distinct active site that catalyzes different chemistry. Comparative analysis identifies other catalysts that contain a shared core protein fold but whose active sites are located in entirely different regions, illustrating a principle predicted from efforts in de novo protein design.
3. Elfamycins: inhibitors of elongation factor-Tu
Samantha M Prezioso, Nicole E Brown, Joanna B Goldberg Mol Microbiol. 2017 Oct;106(1):22-34. doi: 10.1111/mmi.13750. Epub 2017 Aug 9.
Elfamycins are a relatively understudied group of antibiotics that target the essential process of translation through impairment of EF-Tu function. For the most part, the utility of these compounds has been as laboratory tools for the study of EF-Tu and the ribosome, as their poor pharmacokinetic profile and solubility has prevented implementation as therapeutic agents. However, due to the slowing of the antibiotic pipeline and the rapid emergence of resistance to approved antibiotics, this group is being reconsidered. Some researchers are using screens for novel naturally produced variants, while others are making directed, systematic chemical improvements on publically disclosed compounds. As an example of the latter approach, a GE2270 A derivative, LFF571, has completed phase 2 clinical trials, thus demonstrating the potential for elfamycins to become more prominent antibiotics in the future.
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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 ╳
