The Complex of Poly(dG) · Poly(dC) with Arginine: Stabilization of the B Form and Transition to Multistranded Structures

Campos, J. Lourdes; Subirana, Juan A.

doi:10.1080/07391102.1987.10506371

Cited by 8 publications

(2 citation statements)

References 16 publications

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“…In general, studies of protamine interactions have been carried out for double-stranded DNA. These have involved X-ray diffraction, Raman spectra, chemical reaction, and optical detection of magnetic resonance ( − ). Some of the reports are conflicting, but regardless it is now thought that the interaction of protamine and double-stranded DNA involves binding to the major groove with a β-form DNA and β - conformation for the protamine ( , ).…”

Section: Discussionmentioning

confidence: 99%

Protamine-Fragment Peptides Fused to an SV40 Nuclear Localization Signal Deliver Oligonucleotides That Produce Antisense Effects in Prostate and Bladder Carcinoma Cells

et al. 2002

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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 downregulation of the expression of the complementary mRNAs, which in turn resulted in downregulation of protein expression. However, under certain circumstances (predominantly in PC3 cells), incubation of the cells with chloroquine was required to produce antisense activity. Using this strategy, PKC-alpha protein and mRNA expression in T24 and PC3 cells and bcl-2 expression in PC3 cells was reduced by approximately 75 +/- 10% at a minimum concentration of oligomer of 0.25 microM, in combination with 12-15 microM peptide. On the basis of our results, we conclude that arginine-rich peptides of this class may be potentially useful delivery vehicles for the cellular delivery of antisense oligonucleotides. This new strategy may have several advantages over other methods of oligonucleotide delivery and may complement already existing lipid-based technologies.

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Section: Discussionmentioning

confidence: 99%

Protamine-Fragment Peptides Fused to an SV40 Nuclear Localization Signal Deliver Oligonucleotides That Produce Antisense Effects in Prostate and Bladder Carcinoma Cells

et al. 2002

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“…Although, the overall structure of DNA with the repeating tracts of adenine A-tracts DNA belongs to the B-form, there are significant local structural deviation between A-tract DNA and the B-form of random nucleotide sequence (Compos and Subirana, 1987). The pronounced structural feature of A-tract DNA is the presence of a narrow minor groove and bending at the A-tract.…”

Section: Introductionmentioning

confidence: 99%

Molecular dynamics simulation of DNA duplex, analog of PPT (polypurine tract), its conformation and hydration: a theoretical study

Yadav¹,

Yadava

2013

Med Chem Res

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Molecular Dynamics Simulation Study of DNA duplex is reported here in this communication. The duplex is a decamer, which consists of two non-self complementary sequences 5 0 (CAAAGAAAAG) and 5 0 (CTTTTCTTTG). This decamer is a DNA analog of the portion of the polypurine tract, which is a RNA/DNA hybrid that serves as a primer for the synthesis of the non-digestible DNA strand by human immunodeficiency virus reverse transcriptase. The result obtained is compared with the crystal structure of this decamer duplex. The calculations described here using AMBER throw light on the effect of counter ions on the binding of water molecules, within the grooves of the duplex. This study may provide important implications for understanding the functional, energetic, and specificity of the interactions of DNA/RNA with regulatory proteins, pharmaceutical agents, and other ligands.

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Molecular structure of a complete turn of A-DNA

Verdaguer

Aymamı́

Fernandez‐Forner

et al. 1991

Journal of Molecular Biology

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The Complex of Poly(dG) · Poly(dC) with Arginine: Stabilization of the B Form and Transition to Multistranded Structures

Cited by 8 publications

References 16 publications

Protamine-Fragment Peptides Fused to an SV40 Nuclear Localization Signal Deliver Oligonucleotides That Produce Antisense Effects in Prostate and Bladder Carcinoma Cells

Protamine-Fragment Peptides Fused to an SV40 Nuclear Localization Signal Deliver Oligonucleotides That Produce Antisense Effects in Prostate and Bladder Carcinoma Cells

Molecular dynamics simulation of DNA duplex, analog of PPT (polypurine tract), its conformation and hydration: a theoretical study

Molecular structure of a complete turn of A-DNA

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