Solid‐Phase synthesis of peptide nucleic acids

• DOI: 10.1002/psc.310010304
• Publication Date: 2005-05-31T11:38:47Z
• Authors: Leif Christensen; Richard Fitzpatrick; Brian Gildea; Kenneth H. Petersen; Henrik F. Hansen; Troels Koch; Michael Egholm; Ole Buchardt; Peter E. Nielsen; James Coull; Rolf H. Berg
• Keywords: Hexafluorophosphate; Peptide nucleic acid; Oligomer; Peptide Synthesis; Solid-Phase Synthesis; Trifluoromethanesulfonate

Abstract Peptide nucleic acids (PNA) were synthesized by a modified Merrifield method using several improvements. Activation O ‐(benzotriazol‐1‐yl)‐1,1,3,3‐tetramethyluronium hexafluorophosphate in combination with situ neutralization of the resin allowed efficient coupling all four Boc‐protected PNA monomers within 30 min. HPLC analysis crude product obtained from fully automated synthesis model oligomer H‐CGGACTAAGTCCATTGC‐Gly‐NH 2 , indicated an average yield per synthetic cycle 97.1%. N 1 ‐benzyloxycarbonyl‐ 6 3 ‐methylimidazole triflate substantially outperformed acetic anhydride as capping reagent. The resin‐bound PNAs successfully cleaved ‘low–high’ trifluoromethanesulphonic acid procedure.