Synthesis of isotopically labeled Δ2-isopentenylpyrophosphate

Kessler, Michael J.; Clark, James M.

doi:10.1016/0003-2697(73)90301-1

Cited by 1 publication

(1 citation statement)

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“…Procedure B. 34 The crude product obtained from 150 mg of starting alcohol was dissolved in a minimal amount of 1propanol-ammonia-water (9:4:1) and was added to a 2.5 X 18 cm column containing 40 g of silica gel. The silica gel had been preconditioned by stirring in 300 ml of 1:1 concentrated HCl-water for 2 h, standing overnight, decantation of the aqueous layer, washing with water (6 x 300 ml), and drying at 150 °C for 48 h. The column was prewashed and eluted with a 9:4:1 1-propanol-NH4OH-H20 mixture (flow rate 1.5 ml/min), collecting 3-ml fractions.…”

Section: Preincubation (Hr)mentioning

confidence: 99%

Inhibition of squalene synthetase by farnesyl pyrophosphate analogs

Montellano¹,

Wei²,

Castillo³

et al. 1977

J. Med. Chem.

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The pyrophosphates of the following farnesol analogues have been synthesized: 2-methylfarnesol; 7,11-dimethyl-3-ethyl-2,6,10-dodecatrien-1-ol; 3-demethylfarnesol; 4-methylthiofarnesol; 7,11-dimethyl-3-iodo-2,6,10-dodecatrien-1-ol; 7,11-dimethyl02-iodo-2,6,10-dodecatrien-1-ol; 7,11-dimethyldodeca-6,10-dien-2-yn-1-ol; phytol; 3,7,11-trimethyl-2-dodecen-1-ol; 3,7,11-trimethyldodecan-1-ol; and geraniol. The double bonds in all the above compounds were in the E configuration, except phytol, which was a 7:3 mixture of 2E and 2Z isomers. Each of the pyrophosphates inhibits the incorporation of labeled farnesyl pyrophosphate into squalene by a yeast enzyme preparation. Free alcohols and monophosphates are inactive. The analogues, listed in order of decreasing inhibitory strength, are, by kinetic analysis, competitive or mixed inhibitors. Irreversible inhibition is not observed. The results suggest that binding to the enzyme is primarily mediated by the pyrophosphate moiety assisted by relatively nonspecific lipophilic interactions. Decreasing the chain length and saturating double bonds severely reduces binding, while substitution at the 2,3, and 4 positions, and lengthening of the chain, is well tolerated.

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Section: Preincubation (Hr)mentioning

confidence: 99%