Clerocidin
* Please be kindly noted products are not for therapeutic use. We do not sell to patients.
| Category | Antibiotics |
| Catalog number | BBF-00371 |
| CAS | 87501-14-2 |
| Molecular Weight | 696.84 |
| Molecular Formula | C40H56O10 |
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Description
Clerocidin is produced by the strain of Oidiodendron truncatum HL-972. It has anti-gram-positive and negative bacteria activity and inhibits mouse P-388 leukemia.
Specification
| Synonyms | Antibiotic PR-1350 |
| Canonical SMILES | CC1CCC2(C(C1(C)CC3C4(CO4)C5(C(O3)OC6(C(O5)OC(C67CO7)CC8(C(CCC9(C8CCC=C9C=O)C)C)C)O)O)CCC=C2C=O)C |
| InChI | InChI=1S/C40H56O10/c1-23-13-15-33(3)25(19-41)9-7-11-27(33)35(23,5)17-29-37(21-45-37)39(43)31(47-29)49-40(44)32(50-39)48-30(38(40)22-46-38)18-36(6)24(2)14-16-34(4)26(20-42)10-8-12-28(34)36/h9-10,19-20,23-24,27-32,43-44H,7-8,11-18,21-22H2,1-6H3 |
| InChI Key | LKJYEAJRWPUOGW-UHFFFAOYSA-N |
Properties
| Appearance | Colorless Amorphous Powder |
| Antibiotic Activity Spectrum | Gram-positive bacteria; Gram-negative bacteria; neoplastics (Tumor) |
Reference Reading
1. Clerocidin-mediated DNA footprinting discriminates among different G-quadruplex conformations and detects tetraplex folding in a duplex environment
Matteo Nadai, Giovanna Sattin, Giorgio Palù, Manlio Palumbo, Sara N Richter Biochim Biophys Acta. 2013 Oct;1830(10):4660-8. doi: 10.1016/j.bbagen.2013.05.039. Epub 2013 Jun 6.
Background: G-quadruplexes are polymorphic non-canonical nucleic acid conformations involved both in physiological and pathological processes. Given the high degree of folding heterogeneity and comparable conformational stabilities, different G-quadruplex forms can occur simultaneously, hence rendering the use of basic instrumental methods for structure determination, like X-ray diffraction or NMR, hardly useful. Footprinting techniques represent valuable and relatively rapid alternative to characterize DNA folding. The natural diterpenoid clerocidin is an alkylating agent that specifically reacts at single-stranded DNA regions, with different mechanisms depending on the exposed nucleotide. Methods: Clerocidin was used to footprint G-quadruplex structures formed by telomeric and oncogene promoter sequences (c-myc, bcl-2, c-kit2), and by the thrombin binding aptamer. Results: The easy modulability of CL reactivity towards DNA bases permitted to discriminate fully and partially protected sites, highlights stretched portions of the G-quadruplex conformation, and discriminate among topologies adopted by one sequence in different environmental conditions. Importantly, CL displayed the unique property to allow detection of G-quadruplex folding within a duplex context. Conclusions: CL is a finely performing new tool to unveil G-quadruplex arrangements in DNA sequences under genomically relevant conditions. General significance: Nucleic acid G-quadruplex structures are an emerging research field because of the recent indication of their involvement in a series of key biological functions, in particular in regulation of proliferation-associated gene expression. The use of clerocidin as footprinting agent to identify G-quadruplex structures under genomically relevant conditions may allow detection of new G-quadruplex-based regulatory regions.
2. Differential targeting of unpaired bases within duplex DNA by the natural compound clerocidin: a valuable tool to dissect DNA secondary structure
Matteo Nadai, Giorgio Palù, Manlio Palumbo, Sara N Richter PLoS One. 2012;7(12):e52994. doi: 10.1371/journal.pone.0052994. Epub 2012 Dec 28.
Non-canonical DNA structures have been postulated to mediate protein-nucleic acid interactions and to function as intermediates in the generation of frame-shift mutations when errors in DNA replication occur, which result in a variety of diseases and cancers. Compounds capable of binding to non-canonical DNA conformations may thus have significant diagnostic and therapeutic potential. Clerocidin is a natural diterpenoid which has been shown to selectively react with single-stranded bases without targeting the double helix. Here we performed a comprehensive analysis on several non-canonical DNA secondary structures, namely mismatches, nicks, bulges, hairpins, with sequence variations in both the single-stranded region and the double-stranded flanking segment. By analysis of clerocidin reactivity, we were able to identify the exposed reactive residues which provided information on both the secondary structure and the accessibility of the non-paired sites. Mismatches longer than 1 base were necessary to be reached by clerocidin reactive groups, while 1-base nicks were promptly targeted by clerocidin; in hairpins, clerocidin reactivity increased with the length of the hairpin loop, while, interestingly, reactivity towards bulges reached a maximum in 3-base-long bulges and declined in longer bulges. Electrophoretic mobility shift analysis demonstrated that bulges longer than 3 bases (i.e. 5- and 7-bases) folded or stacked on the duplex region therefore being less accessible by the compound. Clerocidin thus represents a new valuable diagnostic tool to dissect DNA secondary structures.
3. Reactivity of clerocidin towards adenine: implications for base-modulated DNA damage
Sara N Richter, Ileana Menegazzo, Matteo Nadai, Stefano Moro, Manlio Palumbo Org Biomol Chem. 2009 Mar 7;7(5):976-85. doi: 10.1039/b819049f. Epub 2009 Jan 23.
Clerocidin is a complex natural molecule which induces DNA damage both directly and through irreversible/reversible poisoning of prokaryotic/eukaryotic topoisomerases II. By analysis of clerocidin reactivity towards adenine and thymine bases, we were able to fully characterize and compare the unique direct reactivity of clerocidin towards the four DNA bases, both in solution and in the DNA context. We showed that thymine was not reactive, while adenine gave a single stable covalent adduct, which was unambiguously identified as the 1,6-dialkylated species by means of modified clerocidin derivatives, modified adenine nucleotides, ESI-MS and multinuclear NMR spectroscopy. The mechanism of formation of the clerocidin adenosine adduct was similar to that occurring with cytosine, while being substantially different from that with guanine. An electrophoresis-based assay was able to highlight the unique ability of clerocidin to chemically discriminate among DNA nucleotides within a nucleic acid sequence. Finally, molecular modelling analysis gave useful indications to solve the apparent contradiction between direct and topoisomerase II-mediated covalent clerocidin reactivity with deoxyadenosine.
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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 ╳
