Tumor selective accumulation of PNA-oligomers conjugated to a somatostatin receptor affine peptide

摘要

Peptide nucleic acids(PNAs)are synthetic DNA analogs in which the sugar phosphate backbone is substituted by neutral amide backbone linkages.Due to this modification,PNAs are achiral and uncharged DNA mimics.Their N-(2-amino-ethyl)-glycine backbone is stable to degradation by proteases as well as nucleases.The purine or pyrimidine bases are linked to the backbone via a methylene carbonyl linker resulting in a geometry similar to the geometry of 'natural' nucleic acids.The hybridization affinity of PNA-oligomers to complementary DNA sequences is higher than the hybridization affinity between analogous DNA oligomers.Consequently,PNA has attracted major attention because of its potential to act as an active component for diagnostic as well as pharmaceutical applications.Due to these properties PNA oligomers are an appropriate choice for pretargeting and in vivo hybridization techniques.However,as with other drugs of high molecular mass,the delivery of PNA,involving passage through the cell membrane,appears to be a general problem.This limited uptake of PNA into cells is still the major obstacle for applying PNA as an antisense agent in clinical applications.