Side-chain deprotection of peptides synthesized onto a beaded cellulose support

Peptide-Perloza beaded cellulose conjugates were synthesized. However, the concentrated TFA solutions usually used for deprotecting peptide-support conjugates were found to be unsuitable for use with Perloza because they destroyed the chromatographic flow properties of the matrix. Conditions for non-destructive (to the matrix) deprotection of the resin-bound peptide were determined in this study. A cocktail of m-cesol/EDT/thioanisole/TMSBr/TFA/DCM (1:1:2:2:15:79 by volume-Reagent D) was found to cleave amino acid side-chain-protecting groups while leaving the chromatographic properties of the peptide-resin unaltered. Although treating aminopropyl Perloza with solutions of TFA in DCM resulted in decrease of amine substitution, treating peptide-Perloza conjugates with identical reagents gave minimal loss of peptide.