Message-Id: <v01540b01aef8ebb83834@[128.197.7.217]>
Date: Wed, 8 Jan 1997 01:16:02 -0500
From: laursen@bu.edu (Richard Laursen)
Subject: Re: PepSyn
To: Recipients of ABRF List <abrf@aecom.yu.edu>
1. The thiobenzyl group is essentially stable to TFA under the usual
cleavage conditions, and my guess is that the 4-methylbenzyl group, while
slightly more labile, would be pretty hard to remove with TFA, too. If you
have any of the 4-methylbenzylpropionic acid on hand, you can treat it with
some TFA and see (e.g., by HPLC or NMR)if anything happens. It probably
wouldn't be too hard to make the trityl derivative from trityl chloride and
mercaptopropionic acid (available from Aldrich), although I don't have a
recipe at hand. Alternatively, you could acylate the N-terminus with
3,3'-dithiodipropionic acid (Aldrich), activating the carboxyl with
diisopropyl carbodiimide or TBTU. After coupling, treat the resin with DTT
or some other reducing agent to generate the thiol, wash, and
deprotect/cleave as usual. You might want to do the reduction at pH 6 to 7
to get efficient cleavage of the disulfide. On the other hand, maybe
deprotection using Reagent R or K, which contain thiols, would be
sufficient.
Be warned that mercaptopropionic acid and dithiodipropionic acid are very
smelly.
2. I don't have an answer for this question.
Richard Laursen
>Two questions for the peptide chemists in the audience.
>
>1. We wish to make a short peptide (7 residues) that contains an
>N-terminal (3-thio)propionic acid residue. It will look like an
>N-terminal Cys without its amino group. Using FastMoc chemistry on an ABI
>430 synthesizer, I propose to add the thiopropionyl "residue" as its
>4-methyl-benzyl-3-thio propionic acid derivative coupled using a normal
>amino acid coupling cycle. Assuming this coupling should work, will the
>4-methyl-benzyl protecting group be removed by TFA using typical FMOC
>deprotection cocktails? This group has been used in t-Boc chemistry to
>make peptides containing this group and is apparently readily removed
>using HF. Alternatively, we could potentially use Trityl-thio-propionate,
>the analog of Trityl-Cys that we currently use for our Cys derivatives
>but this would require obtaining Trityl-3-thio-propionic acid.
>
>2. Does anyone know of a source for Fmoc-homoarginine(Pmc)-OH?
> (Pmc = pentamethylchroman-6-sulphonyl)
>
>Many thanks in advance and New Year's greetings to all, especially the
>"small angel" at the helm of this cyber ship.
>\ml
>
>------------------------------------------------------------------------------
>Mark O. Lively, Ph.D. Voice: 910-716-2969
>Professor of Biochemistry Fax: 910-716-7671
>Bowman Gray School of Medicine email: Lively@mgrp.bgsm.edu
>Wake Forest University
>Winston-Salem, NC 27157
>Home page: http://www.bgsm.edu/molecular_genetics/
>-------------------------------------------------------------------------------