Cysteine Based PNA (CPNA): Design and Synthesis of Novel CPNA Monomers

摘要

Peptide nucleic acids (PNAs), a class of pseudo-peptide DNA mimics, were first introduced by Nielsen and his coworkers in 1991 [1]. PNA oligomers form very stable sequence-specific duplexes with complementary DNA and RNA strands through Watson-Crick base paring, and can bind to duplex DNA by helix invasion [2]. These intriguing properties of PNA implicated great potential for medical and biotechnical applications. Not surprisingly, tremendous efforts on the synthesis of PNAs and their applications have been reported from various scientific groups since their discovery. However, owing presumably to the nature of the simple neutral backbones, most of PNA oligomers have shown poor water-solubility and cell permeability, and these problems have been the main stumbling blocks for PNA application in biomedical fields [3]. To improve these properties, scientists have been attaching cell-membrane-permeabilizing peptide sequences and trying to modify the backbone of PNA, and only a few examples have shown some positive improvement to date [4]. In this report, we introduce our synthesis of novel cysteine based PNA monomers with various alkyl chains attached as shown in Figure 1. Unlike other amino acids, the cysteine possesses the thiol group which complicates the PNA synthesis and that is presumably why cysteine based PNAs have never been reported. We have envisioned that the thiol group of cysteine could take the role as an attachment site for groups designed to improve the physical properties of the PNA oligomers.