Synthesis and Characterisation of Photolabile SPhNPPOC-Protected (R)-MiniPEG Containing Chiral γ-Peptide Nucleic Acid Monomers

Abstract

Peptide nucleic acid (PNA) microarrays are expected to be developed as a new generation of gene detection tools. However, poor water solubility and the limitation of the sequence design of achiral PNA probes mainly hinder their application. Accordingly, (R)-diethylene glycol containing a chiral PNA (miniPEG-γPNA) has been developed to solve these problems. Light-directed synthesis is an effective method to fabricate high-density microarrays. Thiophenyl-2-(2-nitrophenyl)propoxycarbonyl (SPhNPPOC) is a newly synthesised photolabile protective group with high photolytic efficiency. Protecting the PNA monomers with SPhNPPOC may improve the preparation process of PNA microarrays by light-directed synthesis in terms of shortening the deprotection time and restraining side reactions. In this article, SPhNPPOC/carbobenzoxy (Cbz)-protected chiral miniPEG-γPNA monomers are synthesised, and the photo-deprotection rate is approximately twice that of a 2-(2-nitrophenyl)propyloxycarbonyl (NPPOC)-protected monomer. The monomers are expected to be used for the efficient and rapid fabrication of chiral miniPEG-γPNA microarrays through a photolithographic strategy.