Solid-phase synthesis of peptide nucleic acids.

L Christensen; R Fitzpatrick; B Gildea; K H Petersen; H F Hansen; T Koch; M Egholm; O Buchardt; P E Nielsen; J Coull; R H Berg

doi:10.1002/psc.310010304

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PubMed · 9222994

Solid-phase synthesis of peptide nucleic acids.

L Christensen·R Fitzpatrick·B Gildea·K H Petersen·H F Hansen·T Koch·M Egholm·O Buchardt·P E Nielsen·J Coull·R H Berg

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Abstract

Peptide nucleic acids (PNA) were synthesized by a modified Merrifield method using several improvements. Activation by O-[benzotriazol-1-yl]-1,1,3,3-tetramethyluronium hexafluorophosphate in combination with in situ neutralization of the resin allowed efficient coupling of all four Boc-protected PNA monomers within 30 min. HPLC analysis of the crude product obtained from a fully automated synthesis of the model PNA oligomer H-CGGACTAAGTCCATTGC-Gly-NH2, indicated an average yield per synthetic cycle of 97.1%. N1-benzyloxycarbonyl-N6(3)-methylimidazole triflate substantially outperformed acetic anhydride as a capping reagent. The resin-bound PNAs were successfully cleaved by the 'low-high' trifluoromethanesulphonic acid procedure.

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Base Sequence Chromatography, High Pressure Liquid Indicators and Reagents Methods Molecular Structure Nucleic Acids Peptides Resins, Synthetic Solvents Comparative Study Journal Article Research Support, Non-U.S. Gov't

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L Christensen, R Fitzpatrick, B Gildea, K H Petersen, H F Hansen, T Koch, M Egholm, O Buchardt, P E Nielsen, J Coull, R H Berg. Solid-phase synthesis of peptide nucleic acids.. https://doi.org/10.1002/psc.310010304

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