Efficient functional molecule incorporation method to functionalized peptide nucleic acid (PNA): use in synthesis of labeled PNA oligomers

A novel efficient synthetic method for a functionalized PNA (peptide nucleic acid) is described, in which a functional molecule is incorporated in place of a nucleobase. Novel ω-AA–BocPNA–OH (20–24, AA=amino acid) were designed as PNA precursor monomer units into which functional molecules could be incorporated efficiently. Compounds 20–24 reacted quantitatively with OSu (N-hydroxysuccinimidyl) active ester derivatives and isothiocyanate derivatives of commercial functional molecules to give target functionalized PNA monomer units 25–53. Various types of functionalized PNA monomer units could be efficiently incorporated into multiple predetermined positions in a PNA oligomer by SPPS (solid phase peptide synthesis) in the same way as for the four A(Cbz), G(Cbz), C(Cbz), and T PNA monomer units.