Abstract
The objective of this study was to design and synthesize a new CPP-PNA conjugate that would be able to penetrate endothelial cells, bind STAT1 mRNA and thereby block the activity of STAT1 (the Signal Transducer and Activator of Transcription 1), which is important in cases of vessel inflammation. In the course of the study, the TAMRA-PTD-4- Hal(traziole-Gly-PNA)-conjugate was successfully synthesized using a specific 1,3-dipolar Huisgen cycloaddition reaction known as a “click reaction”. The hybridization properties of the conjugate to complementary hSTAT1 mRNA and hSTAT1 ssDNA fragments was verified by capillary electrophoresis (CE). Studies have shown that the attachment of a fluorescence-labeled peptide to a PNA sequence via a 1,2,3-triazole ring did not alter the binding properties of the PNA to the complementary hSTAT1 mRNA or hSTAT1 ssDNA fragments maintaining similar binding affinity. Furthermore, the data obtained suggest that the use of such a conjugate to modulate the activity and expression of STAT1 could provide a new therapeutic strategy for atherosclerosis treatment.
Keywords: Capillary electrophoresis, cell penetrating peptides, click reaction, CPP-PNA conjugate, peptide nucleic acids.
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