Synthesis of Cell-Penetrating Peptide-PNA Constructs.

Small synthetic molecules that can specifically inhibit translation or transcription hold great promise as potential antisense and antigene drugs. The polyamide/peptide nucleic acid (PNA) (1), along with locked (2) and morpholino (3) nucleic acids, is one of the most promising synthetic DNA mimics for these "antisense applications." Extremely high stability in biological fluids (4) as well as in vivo conditions in general, low toxicity, strong and specific pairing with complementary single stranded RNA/DNA are the main advantages of PNA. The heteroduplexes of PNA with RNA or with DNA have remarkably higher stability as compared to naturally occurring homo- or heteroduplexes of RNA and DNA (5). High thermal stability of PNA-containing duplexes is mainly based on the lack of intra-molecular electrostatic repulsion, but also on hydrophobic interactions and less favorable hydration (6). [ABSTRACT FROM AUTHOR]