Hi - There was a prior question on the deprotection of arginine (or d-arginine) protecting groups. Does anyone know of any groups on Arg which can be cleaved by relatively mild acid deprotection (1-2 or up to 5 % TFA/TIPS ?)
I've see three are available as Fmoc-D-Arg, for example Pbf, Pmc, and di-Boc. Does anyone have experience with any of these ?
A more fundamental question is this - do I need to protect Arg when conducting solid phase peptide synthesis with Fmoc-Arg if I use a mild base like NMM ?
The main problems with Arg are (1) incomplete deblocking, especially for peptides with multiple Arg, and (2) alkylation of Trp by the released blocker during cleavage, especially for peptides with multiple Arg and Trp. The Pbf side chain blocker is arguably the best choice for both problems: (1) lability in TFA and (2) facile neutralization of free Pbf by thioanisole scavenger. It's also the most expensive choice.
Fmoc-AA(MIS)-OH may be a slightly better alternative, but it's somewhat experimental and less commercial.
I have published papers about this. You can read my papers. I think this one can help you better:
https://pubmed.ncbi.nlm.nih.gov/35406720/
Yes, you difnitely need to protect arginine as the side reactions will be plenty without protection when conducting solid phase peptide synthesis with Fmoc-Arg.
In my paper above, I cleaved my peptide from the resin only without removing protecting groups in mild acid of DCM/trifluoroethanol (TFE)/acetic acid (AcOH) (35 mL:10 mL:5 mL) while agitating for 3 h. I am not sure what you are trying to do. I agree with Carter that Pbf is the best choice of protecting gourp for Arg. I hope it helps.
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