Issue 5, 2011

DNA-based strategies for blocking HMGB1 cytokine activity: design, synthesis and preliminary in vitro/in vivo assays of DNA and DNA-like duplexes

Abstract

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.

Graphical abstract: DNA-based strategies for blocking HMGB1 cytokine activity: design, synthesis and preliminary in vitro/in vivo assays of DNA and DNA-like duplexes

Supplementary files

Article information

Article type
Paper
Submitted
10 Jan 2011
Accepted
22 Feb 2011
First published
22 Mar 2011

Mol. BioSyst., 2011,7, 1742-1752

DNA-based strategies for blocking HMGB1 cytokine activity: design, synthesis and preliminary in vitro/in vivo assays of DNA and DNA-like duplexes

D. Musumeci, E. M. Bucci, G. N. Roviello, R. Sapio, M. Valente, M. Moccia, M. E. Bianchi and C. Pedone, Mol. BioSyst., 2011, 7, 1742 DOI: 10.1039/C1MB05009E

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