On choosing the right ether for peptide precipitation after acid cleavage.
Methyl tert-butyl ether (MTBE) and diethyl ether (DEE) tend to be regarded as interchangeable for the 'cold ether' workup concluding the final acidolytic cleavage and deprotection step of solid-phase peptide syntheses. However, the use of MTBE to precipitate peptides from strong acid solutions is shown to give rise to t-butyl alkylation byproducts, readily detectable by MALDI-TOF MS. The problem can attain undesirable dimensions in the cleavage of peptide resins containing high proportions of aromatic residues, particularly in peptide nucleic acid (PNA) syntheses. In those cases, DEE workup is advisable, as it consistently leads to cleaner products.
de La Torre
Beatriz G
BG
Department of Experimental and Health Sciences, Pompeu Fabra University, Barcelona Biomedical Research Park, 08003 Barcelona, Spain.
Andreu
David
D
D011232:Chemical Precipitation; D004986:Ether / Q000737:chemistry*; D004987:Ethers / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D008738:Methyl Ethers / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry* / Q000302:isolation & purification
D004987:Ethers; D008738:Methyl Ethers; D010455:Peptides; D004986:Ether; C043243:methyl tert-butyl ether