Microwave-assisted solid-phase peptide synthesis at 60 °C: alternative conditions with low enantiomerization

✍ Scribed by Carina Loffredo; Nilson A. Assunção; Juergen Gerhardt; M. Terêsa Machini Miranda

• Publisher: John Wiley and Sons
• Year: 2009
• Tongue: English
• Weight: 289 KB
• Volume: 15
• Category: Article
• ISSN: 1075-2617
• DOI: 10.1002/psc.1178

✦ Synopsis

Abstract

Several conditions have been used in the coupling reaction of stepwise SPPS at elevated temperature (SPPS‐ET), but we have elected the following as our first choice: 2.5‐fold molar excess of 0.04–0.08 M Boc or Fmoc‐amino acid derivative, equimolar amount of DIC/HOBt (1:1) or TBTU/DIPEA (1:3), 25% DMSO/toluene, 60 °C, conventional heating. In this study, aimed to further examine enantiomerization under such condition and study the applicability of our protocols to microwave‐SPPS, peptides containing L‐Ser, L‐His, L‐Cys and/or L‐Met were manually synthesized traditionally, at 60 °C using conventional heating and at 60 °C using microwave heating. Detailed assessment of all crude peptides (in their intact and/or fully hydrolyzed forms) revealed that, except for the microwave‐assisted coupling of L‐Cys, all other reactions occurred with low levels of amino acid enantiomerization (<2%). Therefore, herein we (i) provide new evidences that our protocols for SPPS at 60 °C using conventional heating are suitable for routine use, (ii) demonstrate their appropriateness for microwave‐assisted SPPS by Boc and Fmoc chemistries, (iii) disclose advantages and limitations of the three synthetic approaches employed. Thus, this study complements our past research on SPPS‐ET and suggests alternative conditions for microwave‐assisted SPPS. Copyright © 2009 European Peptide Society and John Wiley & Sons, Ltd.