Greetings!
I am now working on a F-moc based peptide synthesis having following sequence:
GFARVYMSRSSGWERPSGGNVKCKIGSTENLK (N terminal to C-terminal)
For the cleavage/micro-cleavge, I need to use TFA-m-cresol-thioanisole (86:2:12). However, right now, we are out of thioanisol at our lab. can anyone please tell me, what is the purpose of using thioanisol in this cocktail and which can be a best alternative of thioanisol here?
Thanks in advance
Thioanisol is a scavenger. Scavengers are necessary only for the removal of Pmc, Pbf, and/or Tmob groups.
The employment of thioanisole as a scavenger is recommended for the process of the cleavage of many protecting groups, e.g., benzyloxycarbonyl,91 Tosyl,100 Mts,101 and Mtr.102 Moreover, the properties of thioanisole with respect to circumventing the undesired Met oxidation in the process of peptide side chain global deprotection are also intensively exploited.103
In spite of its versatility thioanisole could indeed induce various uncontrolled modifications on sensitive amino acids, e.g., Met, Trp, Glu, or Asp during acid-mediated peptide side chain global deprotection, particularly in the presence of highly concentrated strong acids such as TFMSA or HF.54 It is, therefore, advisable to avoid the employment of thioanisole for the side chain global deprotection of Trp- and Met-containing peptides directed by HF, or TFMSA in an effort to bypass the alkylation side reactions addressing these residues by thioanisole.
https://www.peptide.com/resources/solid-phase-peptide-synthesis/cleavage-cocktails/
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Low Odor Cleavage Cocktail (Reagent L)
In this cleavage cocktail, dithiothreitol (DTT) replaces the pungent scavengers ethanedithiol (EDT) and thioanisole. Additionally, unlike EDT, DTT does not react readily with the benzophenone moiety of 4-benzoylphenylalanine (Bpa), making Reagent L a preferred cleavage cocktail for Bpa containing peptides.
Thank you so much Dr. Winter and Khalaf. It was very informative and helped me a lot.
In addition to the already mentioned points, I would like to add a couple of my thoughts:
1. If there is a good reason to use any special cleavage cocktail containing those thiol scavangers, then yes there are not many things one can try apart from thiols and TIPS. If you can cleave your peptide with the standard TFA:TIPS:water 95:2.5:2.5 cocktail without any side reactions, there is no need to try anything else.
2. The word 'scavanger' means an 'animal who eats up anything unnecessary'. Similarly these scavangers neither cleave the amino acid side chain protecting groups nor do they help TFA to do so. The real purpose of adding those scavangers is to 'quench' the carbocations/electrophilic species which are generated from all your protecting groups (not just a very few special ones). Usually TIPS (triisopropyl silane) being a good hydride donor (weak Si-H bond) can take care of most of those specie, but at times when you have sensitive groups in your peptide sequence you have to use those thiol scavangers. I have worked with several of peptides containing Met and have never seen any oxidation with the TFA:TIPS:water 95:2.5:2.5 cocktail .
Hope it helps!
Hi Nahar,
Use can also use TFA:TIS:H2O (95:2.5:2.5) cocktail for global deprotection. Its standard cleavage cocktail.
I hope this helps.
Thanks
Since you have no cysteine, try TFA/Phenol/ Tis/H2O (88:5:2:5) .
for ref JOC 1992, 57, 5399
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