Solid-phase synthesis of peptide nucleic acids.
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.
Christensen
L
L
H. C. Orsted Institute, University of Copenhagen, Denmark.
Fitzpatrick
R
R
Gildea
B
B
Petersen
K H
KH
Hansen
H F
HF
Koch
T
T
Egholm
M
M
Buchardt
O
O
Nielsen
P E
PE
Coull
J
J
Berg
R H
RH
D001483:Base Sequence; D002851:Chromatography, High Pressure Liquid; D007202:Indicators and Reagents; D008722:Methods; D015394:Molecular Structure; D009696:Nucleic Acids / Q000138:chemical synthesis* / Q000737:chemistry* / Q000302:isolation & purification; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry* / Q000302:isolation & purification; D012117:Resins, Synthetic; D012997:Solvents
D007202:Indicators and Reagents; D009696:Nucleic Acids; D010455:Peptides; D012117:Resins, Synthetic; D012997:Solvents