I have been synthesising a peptide with the sequence YT(Sar-EEG)IDDP on CTC-resin with an additional depsi-bond between the threonine sidechain and the C-terminus of sarcosine. The proline C-terminus is protected with an allyl ester, and the tyrosine N-terminus with a Teoc-protecting group. Both N-termini in the sequence have been deprotected before doing a mini cleavage (95/2.5/2.5 TFA/TIPS/H2O). The peptide crashes out nicely, but as soon as the ether is evaporated after spinning it down, it becomes this almost plastic-like, insoluble solid. I have tried basic buffers, chaotropic salt, TFA, TEA, formic acid, organic solvents - nothing seems to dissolve it no matter how long I sonicate.
Did anyone have this issue before or has any other suggestions?