An optimized semi-automatic protocol for parallel synthesis of up to 96 peptide nucleic acids (PNA) or PNA-peptide conjugates using Boc-protection strategy has been developed using a robotic system. The approach is illustrated by synthesizing PNA and PNA-peptide libraries varying between 15 and 27 “amino acid” units. The peptides (NLS (nuclear localization signal) or Tat-peptide) were attached to N-terminus of the PNA. The method was found to be far superior to that based on the SPOT / Fmoc protocol by which PNA oligomers are synthesized on a modified cellulose membrane. On a 0.5 micromole scale the method typically yielded 2 mg product of 90% purity by HPLC / MALDI-TOF analysis. This approach is suitable for screening of a large number of PNA and / or peptide sequences for biochemical and biological studies.
Keywords: pna libraries, pna-peptide libraries, boc-protection strategy
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