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Topic: Ziconotide (or MVIIA conotoxin) synthesis  (Read 19677 times)

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Offline nick123

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Ziconotide (or MVIIA conotoxin) synthesis
« on: February 06, 2013, 07:16:37 PM »
Hello all!

I have a project in 5 days about α peptide which comes from snail conus magus called ziconotide... Does anybody know its synthesis??? I 've searched a lot of papers and internet sites of course and i didn't find anything...

Any help is appreciated!!

Offline Arkcon

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Re: Ziconotide (or MVIIA conotoxin) synthesis
« Reply #1 on: February 06, 2013, 10:01:02 PM »
Please start by reading the Forum Rules{click}.  We'd like to see a little more effort from you, and the deadline is your problem, not ours.  Also, I really doubt that you looked everywhere and found nothing.  You know the generalized class of this toxin/medicine, so you should be able to infer the synthesis method.
Hey, I'm not judging.  I just like to shoot straight.  I'm a man of science.

Offline discodermolide

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Re: Ziconotide (or MVIIA conotoxin) synthesis
« Reply #2 on: February 06, 2013, 11:53:27 PM »
Have you tried Google, it's really quite good for this sort of thing! I found lots and lots, 189000 hits. o you may be busy for a while.
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Offline nick123

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Re: Ziconotide (or MVIIA conotoxin) synthesis
« Reply #3 on: February 07, 2013, 12:16:27 PM »
Fisrt of all i am really sorry!!

Secondly i didnt find anything special except this... Its solid phase peptide synthesis method...

http://www.sciencedirect.com/science/article/pii/S0960894X9900699X take a look in the last picture Scheme 1...

Is it the synthesis for ziconotide???

Offline Arkcon

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Re: Ziconotide (or MVIIA conotoxin) synthesis
« Reply #4 on: February 07, 2013, 12:26:55 PM »
Not really, but it is related.  If your university can get you access, it would be a worthwhile read, for you to begin to write about your project.  Meantime, could you humor us by telling us exactly what you know about this class of compound?  What is it, in general terms?  How was it discovered?  How did it get to where it was discovered -- if that makes any sense?
Hey, I'm not judging.  I just like to shoot straight.  I'm a man of science.

Offline nick123

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Re: Ziconotide (or MVIIA conotoxin) synthesis
« Reply #5 on: February 07, 2013, 12:39:44 PM »
Ziconotide is an anagletic compound found in 1980 from Michael McIntosh . Its a polybasic peptide with 25 aminoacids connected with 3 disulfide bridges. Also called snx111 and MVIIA wmega-conotoxin...

Conotoxin are polypeptides of 10-30 aminoacids with 1-3 disulfide bridges....

  It comes from an sea marine poisonus snail called conus magus.

It is also a drug called prialt from ELan company...
« Last Edit: February 07, 2013, 01:30:11 PM by nick123 »

Offline discodermolide

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Re: Ziconotide (or MVIIA conotoxin) synthesis
« Reply #6 on: February 07, 2013, 12:42:19 PM »
Have a look in J. Med. Chem. 2011, doi.org/10.1021/jm201060r, Crail G. J. etalEffects of Cyclization on Stability, Structure, and Activity of α-Conotoxin RgIA at the α9α10 Nicotinic Acetylcholine Receptor and GABAB Receptor.

It tells you how they cyclised the analogues.
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Offline nick123

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Re: Ziconotide (or MVIIA conotoxin) synthesis
« Reply #7 on: February 07, 2013, 12:53:07 PM »
Have a look in J. Med. Chem. 2011, doi.org/10.1021/jm201060r, Crail G. J. etalEffects of Cyclization on Stability, Structure, and Activity of α-Conotoxin RgIA at the α9α10 Nicotinic Acetylcholine Receptor and GABAB Receptor.

It tells you how they cyclised the analogues.

Thanks but i cannot open the paper... it says that i have to pay in order to read it...

Offline Arkcon

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Re: Ziconotide (or MVIIA conotoxin) synthesis
« Reply #8 on: February 07, 2013, 01:16:57 PM »
Great, now this part ...

Its a polybasic peptide with 25 aminoacids connected with 3 disulfide bridges.

What odes that really mean?
Hey, I'm not judging.  I just like to shoot straight.  I'm a man of science.

Offline nick123

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Re: Ziconotide (or MVIIA conotoxin) synthesis
« Reply #9 on: February 07, 2013, 01:26:29 PM »

Offline Arkcon

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Re: Ziconotide (or MVIIA conotoxin) synthesis
« Reply #10 on: February 07, 2013, 01:39:56 PM »
Sorry, a copied image isn't the answer I was looking for.  What's a peptide?
Hey, I'm not judging.  I just like to shoot straight.  I'm a man of science.

Offline nick123

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Re: Ziconotide (or MVIIA conotoxin) synthesis
« Reply #11 on: February 07, 2013, 06:20:35 PM »
Peptides are short chains of amino acid monomers linked by peptide amide bonds.

I didnt find anything yet  :-\

Offline Arkcon

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Re: Ziconotide (or MVIIA conotoxin) synthesis
« Reply #12 on: February 07, 2013, 08:58:36 PM »
You seem to be looking these things up one at a time without troubling yourself to understand the underlying meaning.  But I can play along, at least until some new member or other White Knight character dumps the answer for you.  Therefore ... what else are peptides?  Also, can you answer/look up a few more of my previous questions:

Quote
How was it discovered?  How did it get to where it was discovered -- if that makes any sense?
Hey, I'm not judging.  I just like to shoot straight.  I'm a man of science.

Offline discodermolide

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Re: Ziconotide (or MVIIA conotoxin) synthesis
« Reply #13 on: February 09, 2013, 09:04:09 AM »
I got the Smiles for this compound, non-cyclised. It's enormous, and it's not quite how I would draw the chirality, here it is, feel free to delete it if it is too large.
N[C@H](C(N[C@@H](CCCCN)C(NCC(N[C@@H](CCCCN)C(NCC(N[C@H](C(N[C@@H](CCCCN)C(N[C@H](C(N[C@@H](CO)C(N[C@@H](CCCNC(N)=N)C(N[C@@H](CC(C)C)C(N[C@H](C(N[C@H](C(N[C@H](C(N[C@H](C(N[C@H](C(N[C@@H]([C@H](O)C)C(NCC(N[C@@H](CO)C(N[C@H](C(N[C@@H](CCCNC(N)=N)C(N[C@@H](CO)C(NCC(N[C@@H](CCCCN)C(N[C@H](C(N)=O)CS)=O)=O)=O)=O)=O)CS)=O)=O)=O)=O)CS)=O)CS)=O)CC(O)=O)=O)CC1=CC=C(O)C=C1)=O)CCSC)=O)=O)=O)=O)CS)=O)=O)C)=O)=O)=O)=O)=O)CS
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Offline nick123

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Re: Ziconotide (or MVIIA conotoxin) synthesis
« Reply #14 on: February 10, 2013, 02:25:27 PM »
http://sioc-journal.cn/Jwk_hxxb/EN/abstract/abstract338787.shtml#

Where i can find full this paper??

Also i found this one


Fig. 3. Production of a cyclic bioengineered conopeptide: The peptide toxin parent sequence is initially bioengineered to introduce a N- to C-termini spacer/linker, together with OPG insertion to enable later selective disulfide bond formation. To enable N- to C-cyclization the thioester function group is strategically placed – this may require rearrangement of the linear construct to maximize ligation kinetics. In this example the –C–C– is used as the ligation position, this complies with chemical and kinetic requirements of Native Chemical Ligation. N- to C-termini peptide cyclisation is achieved via intramolecular attack of the C-terminal thioester by the N-terminal cysteine thiol. The resulting intermediate strucutre then undergoes spontaneous ring contraction through S,N acyl migration to form the cyclic peptide backbone – importantly resulting in a native-like peptide bond and the regeneration of the Cys thiol function. The now cyclic peptide is then selectively oxidized, the first control disulfide bond is formed between those existing free thiols, and then a secondary bond occurs with selective OPG deprotection and oxidation.

Is that image what i want???

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