Microwave-assisted TFA cleavage of peptides from Merrifield resin.
Microwave-assisted (MW) reactions are of special interest to the chemical community due to faster reaction times, cleaner reactions and higher product yields. The adaptation of MW to solid phase peptide synthesis resulted in spectacular syntheses of difficult peptides. In the case of Merrifield support, used frequently in synthesis of special peptides, the conditions used in product cleavage are not compatible with off-resin monitoring of the reaction progress. The application of MW irradiation in product removal from Merrifield resin using trifluoroacetic acid (TFA) was investigated using model tetrapeptides and the effects were compared with standard trifluoromethanesulphonic acid (TFMSA) cleavage using elemental analysis as well as chromatographic (HPLC) and spectroscopic (IR) methods. The deprotection of benzyloxycarbonyl and benzyl groups in synthetic bioactive peptides was analyzed using LC-MS and MS/MS experiments. In a 5 min microwave-assisted TFA reaction at low temperature, the majority of product is released from the resin, making the analytical scale MW-assisted procedure a method of choice in monitoring the reactions carried out on Merrifield resin due to the short reaction time and compatibility with HPLC and ESI-MS conditions.
Kluczyk
Alicja
A
Faculty of Chemistry, University of Wroclaw, F. Joliot-Curie 14, 50-383 Wroclaw, Poland. kluczyk@wchuwr.pl
Rudowska
Magdalena
M
Stefanowicz
Piotr
P
Szewczuk
Zbigniew
Z
D000595:Amino Acid Sequence; D002851:Chromatography, High Pressure Liquid; D008872:Microwaves; D010455:Peptides / Q000737:chemistry*; D011137:Polystyrenes / Q000737:chemistry*; D013055:Spectrophotometry, Infrared; D053719:Tandem Mass Spectrometry; D014269:Trifluoroacetic Acid / Q000737:chemistry*
C095039:Merrifield resin; D010455:Peptides; D011137:Polystyrenes; D014269:Trifluoroacetic Acid