DNA-based strategies for blocking HMGB1 cytokine activity: Design, synthesis and preliminary in vitro/in vivo assays of DNA and DNA-like duplexes
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DNA-based strategies for blocking HMGB1 cytokine activity: Design, synthesis and preliminary in vitro/in vivo assays of DNA and DNA-like duplexes
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844 views
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Musumeci D
, Bucci EM,
Roviello GN
, Sapio R, Valente M, Moccia M, Bianchi ME,
Pedone C
Mol Biosyst (ISSN: 1742-206x, 1742-2051, 1742-2051electronic)
,
2011 May;
7(5): 1742-1752.
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Paper type:
Journal Article,
Impact factor:
3.534,
5-year impact factor:
3.705
Url:
http://www.scopus.com/inward/record.url?eid=2-s2.0-79954550870&partnerID=40&md5=0910849612aa81cf202011f723666191
Keywords:
Circular Dna, Heteroduplex, High Mobility Group B1 Protein, Kinked Dna, Lipopolysaccharide, Peptide Nucleic Acid, Animal, Article, Bagg Albino Mouse, Binding Site, Cell Line, Cell Motion, Cell Proliferation, Chemical Structure, Chemically Induced Disorder, Chemistry, Conformation, Drug Antagonism, Drug Effect, Endotoxemia, Metabolism, Mortality, Nucleotide Sequence, Protein Binding, Protein Tertiary Structure, Survival Rate, Base Sequence, Cell Movement, Hmgb1 Protein, Inbred Balb C, Models, Molecular, Molecular Structure, Nucleic Acid Conformation, Nucleic Acid Heteroduplexes, Protein Structure, Time Factors,
Affiliations:
*** IBB - CNR ***
Istituto di Biostrutture e Bioimmagini - CNR, via Mezzocannone 16, 80134 Napoli, Italy
Bionucleon Srl, via Ribes 5, 10010 Colleretto Giacosa (TO), Italy
DIBIT, San Raffaele University, via Olgettina 58, 20132 Milano, Italy
References:
Not available.
DNA-based strategies for blocking HMGB1 cytokine activity: Design, synthesis and preliminary in vitro/in vivo assays of DNA and DNA-like duplexes
In this work we report the design and synthesis of kinked oligonucleotide duplexes as potential inhibitors of HMGB1, a cytokine which triggers a broad range of immunological effects. We found that the designed ligands can interact with HMGB1, as evidenced by circular dichroism spectroscopy, and are able to block some extracellular effects induced by the protein, such as cellular proliferation and migration, as we demonstrated by in vitro biological assays. After selecting the most stable and active kinked duplex, we synthesized the corresponding PNA/DNA chimeric duplex which resulted to be more resistant to enzymatic degradation, and showed a biological activity comparable to that of the natural duplex. Preliminary in vivo assays in a mouse inflammatory model, showed a significant decrease of the mortality after administration of the PNA/DNA kinked duplex to LPS-treated mice. © The Royal Society of Chemistry 2011.
DNA-based strategies for blocking HMGB1 cytokine activity: Design, synthesis and preliminary in vitro/in vivo assays of DNA and DNA-like duplexes
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Peptides of therapeutic interest with antimicrobial and/ or antitumoral activity
Pedone EmiliaMaria
Di Gaetano Sonia
Pirone Luciano
DNA-based strategies for blocking HMGB1 cytokine activity: Design, synthesis and preliminary in vitro/in vivo assays of DNA and DNA-like duplexes
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Total impact factor:
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(
116.117
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Total 5 year impact factor:
118.044
(
118.044
excluding Abstracts).
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