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Extra base pairs

 
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Tim Tyler
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PostPosted: Sat Feb 02, 2008 10:54 am    Post subject: Extra base pairs Reply with quote

News (via s.b.e): Extra base pairs:

"Artificial letters added to life's alphabet"

http://technology.newscientist.com/article/dn13252-artificial-letters-added-to-lifes-alphabet.html

From 64 to 216! What to do with all the extra letters...

Of course, the real fun would come from extra aminos. Start
by adding the common non-coded amino acids, with corresponding
mRNAs - that way at least the new organisms will stand a chance
in the wild without being dependent on dietary supplements.
--
__________
|im |yler http://timtyler.org/ tim@tt1lock.org Remove lock to reply.
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Perry E. Metzger
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PostPosted: Sun Feb 03, 2008 12:57 am    Post subject: Re: [Sci.nanotech] Extra base pairs Reply with quote

Tim Tyler <seemysig@cyberspace.org> writes:
Quote:
News (via s.b.e): Extra base pairs:

"Artificial letters added to life's alphabet"


http://technology.newscientist.com/article/dn13252-artificial-letters-added-to-lifes-alphabet.html

From 64 to 216! What to do with all the extra letters...

Of course, the real fun would come from extra aminos.

That was already done some years ago. It was very cool work, but it
isn't actually of that much immediate use because we can't even design
proteins very deliberately with the existing set of amino
acids. Certainly if we *could* do high quality protein design, this
would open up new capabilities, but we've yet to even scratch the
possibilities the existing amino acids give us.

Quote:
Start by adding the common non-coded amino acids, with corresponding
mRNAs - that way at least the new organisms will stand a chance in
the wild without being dependent on dietary supplements.

Actually, unless they have synthetic pathways for the new amino acids,
they would still need to have them supplied. (Of course, that is
unlikely to matter in practice unless the new amino acids are used in
proteins in critical metabolic pathways).

Perry
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Tim Tyler
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PostPosted: Sun Feb 03, 2008 8:06 am    Post subject: Re: [Sci.nanotech] Extra base pairs Reply with quote

Perry E. Metzger wrote:
Quote:
Tim Tyler <seemysig@cyberspace.org> writes:
News (via s.b.e): Extra base pairs:

"Artificial letters added to life's alphabet"


http://technology.newscientist.com/article/dn13252-artificial-letters-added-to-lifes-alphabet.html
From 64 to 216! What to do with all the extra letters...

Of course, the real fun would come from extra aminos.

That was already done some years ago.

Really? The current paper is here:

Discovery, Characterization, and Optimization of an Unnatural Base Pair
for Expansion of the Genetic Alphabet

http://pubs.acs.org/cgi-bin/abstract.cgi/jacsat/asap/abs/ja078223d.html

It is the only one in PubMed that mentions dSICS and dMMO2.

Quote:
It was very cool work, but it isn't actually of that much immediate
use because we can't even design proteins very deliberately with
the existing set of amino acids.

There's still trial and error approaches - such as GAs.

With extra aminos, there would be many new mutations of
*existing* enzymes, some of which might well be better
than the originals. It would not be difficult to explore
the immediate vicinity of existing solutions for new enzyme
finds - once the appropriate mRNAs were in place.

Quote:
Start by adding the common non-coded amino acids, with corresponding
mRNAs - that way at least the new organisms will stand a chance in
the wild without being dependent on dietary supplements.

Actually, unless they have synthetic pathways for the new amino acids,
they would still need to have them supplied. [...]

Thus either dietary supplements, or the use of common non-coded amino
acids - which can be obtained from sources such as animal flesh.

Synthetic routes in bacteria would be needed in the long term -
otherwise the dietary supplements would wind up costing too much.
--
__________
|im |yler http://timtyler.org/ tim@tt1lock.org Remove lock to reply.
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Bob
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PostPosted: Sun Feb 10, 2008 11:16 pm    Post subject: Re: [Sci.nanotech] Extra base pairs Reply with quote

On Sat, 02 Feb 2008 18:57:51 -0000, "Perry E. Metzger"
<perry@piermont.com> wrote:

Quote:


Tim Tyler <seemysig@cyberspace.org> writes:
News (via s.b.e): Extra base pairs:

"Artificial letters added to life's alphabet"


http://technology.newscientist.com/article/dn13252-artificial-letters-added-to-lifes-alphabet.html

From 64 to 216! What to do with all the extra letters...

Of course, the real fun would come from extra aminos.

That was already done some years ago.

Yes. Apparently what is new here is some specifics, and the quality of
this particular pair.

This pair does not use hydrogen-bonding to provide pairing, but rather
only a hydrophobic matching. One advantage they note of this is that
the new bases are less likely to cause problems by mispairing with the
natural bases. The error rates with natural bases are a serious
problem, that nature deals with in very complex ways. Fitting more
bases into that same system -- with good accuracy -- may be very
challenging.

At the end, they say:
"Our characterization of the d5SICS:dMMO2 heteropair
demonstrates that its synthesis and extension are both relatively
efficient and selective. The pair compares favorably with all
previously characterized unnatural base pair candidates for
which relevant kinetic data are available."

They also suggest that their approach can be used to develop better
pairs. (They do note that one of their new bases tends to pair with
self.)


Looks like a small step in an ongoing process.


Quote:
It was very cool work,

:-)

Indeed, Kool, who has done much of the work on novel base pairs, has
praised it.

bob
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