Synthesis and Hybridization Studies of a New CPP-PNA Conjugate as a Potential Therapeutic Agent in Atherosclerosis Treatment
Monika Wojciechowska, Jaroslaw Ruczynski, Piotr Rekowski, Magdalena Alenowicz, Piotr Mucha, Malgorzata Pieszko, Anna Miszka, Michal Dobkowski and Hans Bluijssen
Affiliation: Department of Chemistry of Bioactive Compounds, Faculty of Chemistry, University of Gdansk, Wita Stwosza 63, 80-952 Gdansk, Poland.
Keywords: Capillary electrophoresis, cell penetrating peptides, click reaction, CPP-PNA conjugate, peptide nucleic acids.
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.
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