In a peptide nucleic acid (PNA), the base sequences are arranged onto a backbone of repeating units of N-(2-amino-ethyl) glycine instead of on phosphodiester-linked riboses. PNA is a promising platform for the design of novel chemical probes because PNAs can form complementary base pairs with DNA and RNA that exhibit high enzymatic stability. Described herein is a pot-economical liquid-phase PNA synthesis achieved using a soluble tag-assisted method. Intramolecular trapping of the activated PNA monomer occurs much faster than the undesired intermolecular "double hit". Consequently, excess PNA monomers do not have to be rinsed away after each coupling, enabling one-pot coupling and deprotection without the need for precipitation.