I would to perform a C-terminal amidation on my peptides. I believe the answer lies in the type of resin being used. Currently I have Rink Amide MBHA and Wang and resins in stock.
If you use Rink Amide MBHA resin, you do not have to perform any C-term amidation. When you cleave your peptide from Rink amide-MBHA resin, it will give you C-terminus amide by default.
One option is to directly couple the C-terminus using a "safety-catch resin". Another option would be to cleave your peptide without deprotecting the amino acid side chains (either by using benzyl/Cbz side chain protecting groups on Wang resin or by using mild acidic cleavage on chlorotrityl resin), and then label your C-terminus and finally deprotecting.
If you use Rink Amide MBHA resin, you do not have to perform any C-term amidation. When you cleave your peptide from Rink amide-MBHA resin, it will give you C-terminus amide by default.
In SPPS the type of resin is fundamental and define the C-terminus. With Wang resin only carboxi peptides is obtained. With Ring amide MBHA resin only caboxamide peptides is obtaing. With Trt resin carboxi protected (lateral chain) peptides is obtaing. With HMBA resin carboxi salt, carboxamides, etc protected peptides is obtained. For you, the use of Ring amide MBHA resin and cleavaje with, TFA / TIS / H2O permit obtain the desprotected carboxamide peptide.
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