PMID: 11906253Mar 22, 2002Paper

Protamine-fragment peptides fused to an SV40 nuclear localization signal deliver oligonucleotides that produce antisense effects in prostate and bladder carcinoma cells

Bioconjugate Chemistry
Luba BenimetskayaC A Stein

Abstract

The development of antisense technology has focused on improving methods for oligonucleotide delivery into cells. In the present work, we describe a novel strategy for oligonucleotide delivery based on a bifunctional peptide composed of a C-terminal protamine-fragment that contains a DNA-binding domain and an N-terminal nuclear localization signal sequence derived from the SV40 large-T antigen (The sequences of two of the peptides are R6WGR6-PKKKRKV [s-protamine-NLS] and R4SR6FGR6VWR4-PKKKRKV [l-protamine-NLS]). We demonstrated, by intrinsic fluorescence quenching, that peptides of this class form complexes with oligodeoxynucleotides. To evaluate delivery, we used a 20-mer phosphorothioate oligomer (Isis 3521) targeted to the 3'-untranslated region of the PKC-alpha mRNA and G3139, an 18-mer phosphorothioate targeted to the first six codons of the human bcl-2 open reading frame, and complexed them with either of two peptides (s- or l-protamine-NLS). These peptides bind to and deliver antisense oligonucleotides to the nucleus of T24 bladder and PC3 prostate cancer cells, as demonstrated by confocal microscopy. Furthermore, as shown by Western and Northern blotting, the peptide-oligonucleotide complexes produced excellent downregu...Continue Reading

References

Jun 1, 1986·Journal of Biomolecular Structure & Dynamics·L C PuigjanerJ A Subirana
Aug 1, 1987·Journal of Biomolecular Structure & Dynamics·J L Campos, J A Subirana
Jan 6, 1999·Proceedings of the National Academy of Sciences of the United States of America·M A ZantaJ P Behr
Jun 7, 2000·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·I LebedevaM Vilenchik

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Citations

Nov 26, 2002·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·Nathalie Dias, C A Stein
Nov 14, 2008·Proceedings of the National Academy of Sciences of the United States of America·Pinal C PatelChad A Mirkin
Jun 20, 2008·Organic & Biomolecular Chemistry·Kelly M StewartShana O Kelley
Jul 29, 2003·Journal of Pharmaceutical Sciences·Melanie A Lysik, Susanna Wu-Pong
Jan 31, 2012·Journal of Controlled Release : Official Journal of the Controlled Release Society·Marcelo A S ToledoAdriano R Azzoni
Aug 5, 2003·The Journal of Gene Medicine·Yoon Jeong ParkVictor C Yang
Jul 21, 2005·Bioconjugate Chemistry·Johannes WinklerChristian R Noe

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