Oligomycin A
Names
IUPAC name
(1R,4E,5'S,6S,6'S,7R,8S,10R,11R,12S,14R,15S,16R,18E,20E,22R,25S,27R,28S,29R)-22-ethyl-7,11,14,15-tetrahydroxy-6'-[(2R)-2-hydroxypropyl]-5',6,8,10,12,14,16,28,29-nonamethyl-3',4',5',6'-tetrahydro-3H,9H,13H-spiro[2,26-dioxabicyclo[23.3.1]nonacosa-4,18,20-triene-27,2'-pyran]-3,9,13-trione
Other names
Oligomycin
Identifiers
3D model (JSmol)
ChEBI
ChemSpider
ECHA InfoCard 100.014.334 Edit this at Wikidata
EC Number
  • 215-767-9
MeSH Oligomycins
RTECS number
  • RK3325000
UNII
  • InChI=1S/C46H76O11/c1-13-34-18-16-14-15-17-28(4)42(51)45(12,54)43(52)32(8)40(50)31(7)39(49)30(6)38(48)27(3)19-22-37(47)55-41-29(5)35(21-20-34)56-46(33(41)9)24-23-26(2)36(57-46)25-44(10,11)53/h14-16,18-19,22,26-36,38,40-42,48,50-51,53-54H,13,17,20-21,23-25H2,1-12H3/b15-14+,18-16-,22-19+/t26-,27-,28+,29+,30+,31-,32-,33-,34+,35?,36-,38-,40+,41+,42+,45+,46-/m1/s1 checkY
    Key: QBAMBSAJEFIQBK-GJHUHQBXSA-N checkY
  • InChI=1S/C46H76O11/c1-13-34-18-16-14-15-17-28(4)42(51)45(12,54)43(52)32(8)40(50)31(7)39(49)30(6)38(48)27(3)19-22-37(47)55-41-29(5)35(21-20-34)56-46(33(41)9)24-23-26(2)36(57-46)25-44(10,11)53/h14-16,18-19,22,26-36,38,40-42,48,50-51,53-54H,13,17,20-21,23-25H2,1-12H3/b15-14+,18-16-,22-19+/t26-,27-,28+,29+,30+,31-,32-,33-,34+,35?,36-,38-,40+,41+,42+,45+,46-/m1/s1
    Key: QBAMBSAJEFIQBK-GJHUHQBXBC
  • Key: QBAMBSAJEFIQBK-GJHUHQBXSA-N
  • C[C@](C)(O)C[C@H]1O[C@@]2(CC[C@H]1C)O[C@H]3CC[C@@H](CC)/C=C\C=C\C[C@H](C)[C@H](O)[C@](C)(O)C(=O)[C@H](C)[C@@H](O)[C@H](C)C(=O)[C@@H](C)[C@H](O)[C@H](C)/C=C/C(=O)O[C@H]([C@H]2C)[C@H]3C
Properties
C45H74O11
Molar mass 791.062 g/mol
Hazards
Safety data sheet (SDS) MSDS at Fermentek
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
checkY verify (what is checkY☒N ?)

Oligomycins are macrolides created by Streptomyces that are strong antibacterial agents but are often poisonous to other organisms, including humans.

Function

Oligomycins have use as antibiotics. However, in humans, they have limited or no clinical use due to their toxic effects on mitochondria and ATP synthase.[1]

Oligomycin A is an inhibitor of ATP synthase.[1] In oxidative phosphorylation research, it is used to prevent state 3 (phosphorylating) respiration. Oligomycin A inhibits ATP synthase by blocking its proton channel (FO subunit), which is necessary for oxidative phosphorylation of ADP to ATP (energy production). The inhibition of ATP synthesis by oligomycin A will significantly reduce electron flow through the electron transport chain; however, electron flow is not stopped completely due to a process known as proton leak or mitochondrial uncoupling.[2] This process is due to facilitated diffusion of protons into the mitochondrial matrix through an uncoupling protein such as thermogenin, or UCP1.

Administering oligomycin to rats can result in very high levels of lactate accumulating in the blood and urine.[3]

Oligomycins[4]
  R1 R2 R3 R4 R5
Oligomycin A CH3 H OH H,H CH3
Oligomycin B CH3 H OH O CH3
Oligomycin C CH3 H H H,H CH3
Oligomycin D
(Rutamycin A) 		H H OH H,H CH3
Oligomycin E CH3 OH OH O CH3
Oligomycin F CH3 H OH H,H CH2CH3
Rutamycin B H H H H,H CH3
44-Homooligomycin A CH2CH3 H OH H,H CH3
44-Homooligomycin B CH2CH3 H OH O CH3

References

  1. ^ a b Mackieh R, Al-Bakkar N, Kfoury M, Roufayel R, Sabatier JM, Fajloun Z (March 2023). "Inhibitors of ATP Synthase as New Antibacterial Candidates". Antibiotics. 12 (4): 650. doi:10.3390/antibiotics12040650. PMC 10135114. PMID 37107012.
  2. ^ Jastroch M, Divakaruni AS, Mookerjee S, Treberg JR, Brand MD (2010). "Mitochondrial proton and electron leaks". Essays in Biochemistry. 47 (1): 53–67. doi:10.1042/bse0470053. PMC 3122475. PMID 20533900.
  3. ^ Kramar R, Hohenegger M, Srour AN, Khanakah G (December 1984). "Oligomycin toxicity in intact rats". Agents and Actions. 15 (5–6): 660–663. doi:10.1007/BF01966788. PMID 6532186. S2CID 7837164.
  4. ^ Nakata M, Ishiyama T, Akamatsu S, Hirose Y, Maruoka H, Suzuki R, Tatsuta K (1995). "Synthetic studies on oligomycins. Synthesis of the oligomycin B spiroketal and polypropionate portions". Bulletin of the Chemical Society of Japan. 68 (3): 967–89. doi:10.1246/bcsj.68.967.
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