Details

Autor(en) / Beteiligte

• Pernille Tofteng, A.
• Pedersen, Søren L.
• Staerk, Dan
• Jensen, Knud J.

Titel

Effect of Residual Water and Microwave Heating on the Half-Life of the Reagents and Reactive Intermediates in Peptide Synthesis

Ist Teil von

• Chemistry : a European journal, 2012-07, Vol.18 (29), p.9024-9031

Ort / Verlag

Weinheim: WILEY-VCH Verlag

Erscheinungsjahr

2012

Quelle

Wiley-Blackwell Journals

Beschreibungen/Notizen

• 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. Peptide couplings: Systematic studies of the rate of formation of activated esters by NMR spectroscopy (see figure) and their N‐acylation during peptide synthesis were performed by using 13C‐labeled Boc‐Ala‐OH. A study of the amount of residual water in the solvents revealed a significant effect on the electrophilic reagents and intermediates.