Issue 30, 2013

Hairpin ODN-based ligands as potential inhibitors of HMGB1 cytokine activity

Abstract

We here report the design, synthesis, and biological activity of a kinked hairpin-loop DNA acting at low nM concentrations as a strong inhibitor of HMGB1 (High-Mobility Group Box-1), a nuclear protein with cytokine activity in a number of inflammatory diseases. Lead compound optimization has been realized by inserting different oligo-ethylene glycol spacers at the 5′-end and loop positions of the natural hairpin DNA, in order to improve its enzymatic stability and structuring capability, as well as its overall pharmacokinetic properties. Thermal stability data as well as activity assays proved that the ODN which contained two hexa-ethylene glycol spacers, one at the 5′-end and the other in the loop, was the best candidate to inhibit HMGB1. Plasma stability assays and hydrodynamic volume measurements afforded further encouraging results in view of future in vivo evaluation of the optimized ligand.

Graphical abstract: Hairpin ODN-based ligands as potential inhibitors of HMGB1 cytokine activity

Article information

Article type
Paper
Submitted
05 Mar 2013
Accepted
01 May 2013
First published
02 May 2013

RSC Adv., 2013,3, 12176-12184

Hairpin ODN-based ligands as potential inhibitors of HMGB1 cytokine activity

D. Musumeci, G. N. Roviello, D. Montesarchio, R. Sapio, M. Valente, V. Anrò and E. M. Bucci, RSC Adv., 2013, 3, 12176 DOI: 10.1039/C3RA41915K

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