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What is bioguide fractionation?

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Frederick Williams

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Jul 1, 2009, 8:17:34 AM7/1/09
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What is bioguide fractionation?
Tia.
--
Which of the seven heavens / Was responsible her smile /
Wouldn't be sure but attested / That, whoever it was, a god /
Worth kneeling-to for a while / Had tabernacled and rested.

Tom McCloud

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Jul 1, 2009, 5:43:20 PM7/1/09
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On Wed, 01 Jul 2009 13:17:34 +0100, Frederick Williams
<frederick...@tesco.net> wrote:
>What is bioguide fractionation?
>Tia.

Say, for example, you are trying to find a new drug to treat
Staphylococcus aureus infection. You can grow the microbe in Petri
dishes or microtiter plates, and then add substances to the S.aureus
to see whether it is killed. The substances you test could be
things like extracts of plants, or extracts of microbial
fermentations, which are complicated mixtures of many chemicals. Then,
say for example, one of those extracts which you test is very
effective in killing the S.aureus. So your job next is to figure out
what compound is present in the extract which is responsible for
killing the microbe. You do that by using the process named
activity-directed, or bioguided fractionation. You take that active
extract, pass it down a silica chromatography column, and generate
10 fractions ranging from least polar through most polar molecules.
You then test every one of those 10 fractions to see whether they kill
S.aureus. If you are lucky, only one or two of those column
fractions posses the S.aureus-killing compound, but most likely it is
still not clean enough to determine its structure. So you do another
column chromatographic separation using only the bioactive fraction to
generate 10 additional fractions from it, and you test the killing
activity of each of those. So in each step along the process you
allow the biological activity, i.e. killing S.aureus, to direct you
toward the material which has the biological activity.

Activity-directed fractionation is an important principle in finding
substances which have a biological activity, but are present in
mixtures in such extremely tiny amounts you would not likely ever find
them by strictly chemical means. Taxol, the anticancer drug, is
present in Taxus brevifolia, the Pacific yew, at 0.002%.
Tom McCloud

Frederick Williams

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Jul 2, 2009, 5:26:27 AM7/2/09
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Thank you!

danger...@gmail.com

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Jul 3, 2009, 1:34:37 PM7/3/09
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On Jul 1, 2:43 pm, Tom McCloud <tommc...@gmail.com> wrote:
> Activity-directed fractionation is an important principle in finding
> substances which have a biological activity, but are present in
> mixtures in such extremely tiny amounts you would not likely ever find
> them by strictly chemical means.  

Thanks for a clear explanation.

Turns out that I participated in an experiment 35 years ago,
fractionating crude oil and looking for the fraction that was most
potent in inducing aryl hydroxylases in fish. The method didn't have a
name then, I guess.

DB

Marvin

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Jul 4, 2009, 10:38:21 AM7/4/09
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It may have been action spectroscopy or a variant. I don't
know when that method was first used, but I knew about it
some 50 years ago.

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