Effect of residual water and microwave heating on the half-life of the reagents and reactive intermediates in peptide synthesis.
Precise microwave heating has changed the way many small molecules are being synthesized and, currently, the field of solid-phase peptide synthesis is undergoing dramatic changes owing to the use of microwave heating. To fully reap the benefits of precise microwave heating for the formation of amide bonds in peptide synthesis, it is important to understand the kinetics of formation and break-down of activated esters and their N-acylation of the nascent peptide chain at elevated temperatures. Herein, we present systematic studies of, first, the rate of formation of activated esters by NMR spectroscopy and, second, their N-acylation during peptide synthesis. A study of the amount of residual water in the solvents revealed a significant effect on electrophilic reagents and intermediates. This observation was expanded into a general study of microwave heating in peptide synthesis.
IGM, Faculty of Science, University of Copenhagen, Thorvaldsensvej 40, 1871 Frederiksberg, Denmark.
A Pernille
AP
Tofteng
Søren L
SL
Pedersen
Dan
D
Staerk
Knud J
KJ
Jensen
D006207:Half-Life; D006361:Heating; D007202:Indicators and Reagents / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008872:Microwaves; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry*; D012997:Solvents / Q000737:chemistry*
D007202:Indicators and Reagents; D010455:Peptides; D012997:Solvents