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Topic: Resin Cleavage without Deprotection  (Read 2869 times)

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Offline Rose911

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Resin Cleavage without Deprotection
« on: November 07, 2013, 07:44:29 AM »
Hi there,

I am currently looking for a new method in which I can leave the protecting groups intact on my peptide, once synthesised so that once the resin is cleaved I am left with an exposed acid group. The only way I have thought of so far is to cleave the resin and leave the protecting groups intact, however all methods seem to show cleavage of the resin and protecting groups in the same step. Does anybody know a method of cleaving the resin whilst maintaining the fmoc protecting groups on my peptide?

Thanks  :)

Offline sjb

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Re: Resin Cleavage without Deprotection
« Reply #1 on: November 07, 2013, 08:25:34 AM »
Hi there,

I am currently looking for a new method in which I can leave the protecting groups intact on my peptide, once synthesised so that once the resin is cleaved I am left with an exposed acid group. The only way I have thought of so far is to cleave the resin and leave the protecting groups intact, however all methods seem to show cleavage of the resin and protecting groups in the same step. Does anybody know a method of cleaving the resin whilst maintaining the fmoc protecting groups on my peptide?

Thanks  :)

What resin are you using? Fmoc tends to be deprotected with base, I believe. So if you can find some non-basic means of removing the resin that would help.

Offline Oxime

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Re: Resin Cleavage without Deprotection
« Reply #2 on: November 08, 2013, 07:40:33 AM »
To clarify, Fmoc-protected solid phase synthesis utilizes acid-cleavable side chain protecting groups (e.g. Boc, trityl, t-butyl) and Fmoc protection of the primary amine on the amino acid. The Fmoc group is base cleavable, but this only removes the N-terminal protection.

Most resins in Fmoc SPPS are acid cleavable as well, so that removal of the completed chain by resin also universally deprotects the side chains. If for some reason you want to keep the protecting groups on, you need a resin that's cleaved by neither acidic conditions or basic conditions.

I think there are some orthogonal resins out there, but they might be tricky to find. I seem to recall something about a light-cleavable resin at one point.

Offline Rose911

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Re: Resin Cleavage without Deprotection
« Reply #3 on: November 08, 2013, 11:24:26 AM »
I have used Fmoc-Asp(OtBu)-OH resin. I built my peptide C to N terminus from the resin, I however need the carboxyl group available to react with another protein, to mimic a natural process.
I thought that cleavage of the resin alone using something such as TFA would prevent any unwanted Fmoc deprotections and would be easier than, cleaving everything re-protecting and attempting to isolate the carboxyl group.
I did not realise that the Fmoc groups would be cleaved also via treatment of TFA?

Offline Oxime

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Re: Resin Cleavage without Deprotection
« Reply #4 on: November 11, 2013, 09:53:55 AM »
The Fmoc group is not removed by treatment with acid. If you want an unprotected side chain carboxylate, I'm not sure what your issue is?

The side chain carboxylate will be deprotected upon cleavage from resin. If you want to be able to selectively deprotect it after resin cleavage for some reason, there are commercially available amino acids that are orthogonally deprotected. I'd recommend looking through the Nova BioChem amino acid catalogue.

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