Bottromycin information

Bottromycin A2
Names
	Other names Bottromycin A(2); Bottromycic A2 acid, methyl ester
Identifiers
CAS Number	15005-62-6;
3D model (JSmol)	Interactive image;
ChemSpider	26365309;
PubChem CID	3081434;
	InChI InChI=1S/C42H62N8O7S/c1-23(2)30-36(53)49-33(41(5,6)7)35(44-22-28(51)50-19-17-24(3)32(50)38(55)46-30)48-34(42(8,9)10)39(56)47-31(25(4)26-15-13-12-14-16-26)37(54)45-27(21-29(52)57-11)40-43-18-20-58-40/h12-16,18,20,23-25,27,30-34H,17,19,21-22H2,1-11H3,(H,44,48)(H,45,54)(H,46,55)(H,47,56)(H,49,53)/t24-,25+,27-,30+,31+,32+,33-,34-/m1/s1; InChI=1/C42H62N8O7S/c1-23(2)30-36(53)49-33(41(5,6)7)35(44-22-28(51)50-19-17-24(3)32(50)38(55)46-30)48-34(42(8,9)10)39(56)47-31(25(4)26-15-13-12-14-16-26)37(54)45-27(21-29(52)57-11)40-43-18-20-58-40/h12-16,18,20,23-25,27,30-34H,17,19,21-22H2,1-11H3,(H,44,48)(H,45,54)(H,46,55)(H,47,56)(H,49,53)/t24-,25+,27-,30+,31+,32+,33-,34-/m1/s1 Key: KSIZLOPUXFSFNR-XZNJZDOZBX;
	SMILES C[C@@H]1CCN2[C@@H]1C(=O)N[C@H](C(=O)N[C@H](/C(=N/[C@H](C(=O)N[C@@H]([C@@H](C)C3=CC=CC=C3)C(=O)N[C@H](CC(=O)OC)C4=NC=CS4)C(C)(C)C)/NCC2=O)C(C)(C)C)C(C)C;
Properties
Chemical formula	C42H62N8O7S
Molar mass	823.05608 g.mol−1
	Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). Infobox references

Bottromycin is a macrocyclic peptide with antibiotic activity. It was first discovered in 1957 as a natural product isolated from Streptomyces bottropensis.^[1] It has been shown to inhibit methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci (VRE) among other Gram-positive bacteria and mycoplasma.^[2] Bottromycin is structurally distinct from both vancomycin, a glycopeptide antibiotic, and methicillin, a beta-lactam antibiotic.

Bottromycin binds to the A site of the ribosome and blocks the binding of aminoacyl-tRNA, therefore inhibiting bacterial protein synthesis.^[3] Although bottromycin exhibits antibacterial activity in vitro, it has not yet been developed as a clinical antibiotic, potentially due to its poor stability in blood plasma.^[2] To increase its stability in vivo, some bottromycin derivatives have been explored.^[2]

The structure of bottromycin contains a macrocyclic amidine as well as a thiazole ring. The absolute stereochemistry at several chiral centers has been determined as of 2009.^[4] In 2012, a three-dimensional solution structure of bottromycin was published.^[5] The solution structure revealed that several methyl groups are on the same face of the structure.

Bottromycin falls within the ribosomally synthesized and post-translationally modified peptide class of natural product.^[6]

^ Waisvisz, J. M. (1957). "Bottromycin. I. A New Sulfur-containing Antibiotic". Journal of the American Chemical Society. 79 (16): 4520–4521. doi:10.1021/ja01573a072.
^ ^a ^b ^c Kobayashi, Yutaka; et al. (2010). "Bottromycin derivatives: Efficient chemical modifications of the ester moiety and evaluation of anti-MRSA and anti-VRE activities". Bioorganic & Medicinal Chemistry Letters. 20 (20): 6116–6120. doi:10.1016/j.bmcl.2010.08.037. PMID 20833545.
^ Otaka, T.; A. Kaji (1976). "Mode of action of bottromycin A2. Release of aminoacyl- or peptidyl-tRNA from ribosomes". Journal of Biological Chemistry. 251 (8): 2299–2306. doi:10.1016/S0021-9258(17)33586-X. PMID 770464.
^ Shimamura, Hiroyuki; et al. (2009). "Structure Determination and Total Synthesis of Bottromycin A2: A Potent Antibiotic against MRSA and VRE". Angewandte Chemie International Edition. 48 (5): 914–917. doi:10.1002/anie.200804138. PMID 19115340.
^ Gouda, Hiroaki; et al. (2012). "Three-dimensional solution structure of bottromycin A2: a potent antibiotic active against methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococci". Chem. Pharm. Bull. 60 (2): 169–171. doi:10.1248/cpb.60.169. PMID 22293474.
^ Cite error: The named reference Huo was invoked but never defined (see the help page).

[Waisvisz-1] Waisvisz, J. M. (1957). "Bottromycin. I. A New Sulfur-containing Antibiotic". Journal of the American Chemical Society. 79 (16): 4520–4521. doi:10.1021/ja01573a072.

[Kobayashi-2] Kobayashi, Yutaka; et al. (2010). "Bottromycin derivatives: Efficient chemical modifications of the ester moiety and evaluation of anti-MRSA and anti-VRE activities". Bioorganic & Medicinal Chemistry Letters. 20 (20): 6116–6120. doi:10.1016/j.bmcl.2010.08.037. PMID 20833545.

[Otaka-3] Otaka, T.; A. Kaji (1976). "Mode of action of bottromycin A2. Release of aminoacyl- or peptidyl-tRNA from ribosomes". Journal of Biological Chemistry. 251 (8): 2299–2306. doi:10.1016/S0021-9258(17)33586-X. PMID 770464.

[Shimamura-4] Shimamura, Hiroyuki; et al. (2009). "Structure Determination and Total Synthesis of Bottromycin A2: A Potent Antibiotic against MRSA and VRE". Angewandte Chemie International Edition. 48 (5): 914–917. doi:10.1002/anie.200804138. PMID 19115340.

[Gouda-5] Gouda, Hiroaki; et al. (2012). "Three-dimensional solution structure of bottromycin A2: a potent antibiotic active against methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococci". Chem. Pharm. Bull. 60 (2): 169–171. doi:10.1248/cpb.60.169. PMID 22293474.

[Huo-6] Cite error: The named reference Huo was invoked but never defined (see the help page).

Bottromycin information

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