ORIGINAL ARTICLES  CELLULAR AND MOLECULAR ADVANCES IN THE STUDY OF INFLAMMATION 

Minerva Biotecnologica 2004 June;16(2):145-9

Copyright © 2004 EDIZIONI MINERVA MEDICA

language: English

New trends for the development of novel decoy molecules against nuclear factor kappa-B (NF-kB) transcription factor

Gambari R.

¹ Biotechnology Center, University of Ferrara, Ferrara, Italy, Interdisciplinary Center for the Study of Inflammation (ICSI), University of Ferrara, Ferrara, Italy, Department of Biochemistry and Molecular Biology, University of Ferrara, Ferrara, Italy

Transcription fac­tor ­decoy (TFD) phar­ma­co­ther­a­py ­against nucle­ar fac­tor kap­pa B (NF-kB) pro­teins ­appears to be an impor­tant strat­e­gy for ther­a­py of inflam­ma­to­ry dis­eas­es, ­since NF-kB is deep­ly ­involved in the pro­cess of inflam­ma­tion. In ­this ­short ­review, we ­describe report­ed ­data on the ­effects of pep­tide nucle­ic ­acids (PNAs)-DNA chi­me­ras as TFD mole­cules. These mole­cules are com­posed of a ­part of PNA and a ­part of DNA, ­obey the Watson-Crick ­rules on bind­ing to com­ple­men­tary DNA and RNA and dis­play ­water sol­u­bil­ity. With ­respect to TFD ­approach, prom­is­ing ­results ­have ­been ­obtained ­using dou­ble-strand­ed PNA-DNA chi­me­ras mim­ick­ing the NF-kB and Sp1 bind­ing ­sites ­present with­in the ­long ter­mi­nal ­repeat (LTR) of the ­human immu­no­def­i­cien­cy ­type 1 ­virus (HIV-1). In addi­tion, PNA-DNA chi­me­ras are ­more resist­ant ­than DNA/DNA ­hybrids to nucle­as­es and are suit­able for deliv­ery ­with cat­ion­ic lipo­somes and micro­spheres. In the ­near ­future chi­mer­ic mole­cules ­could be devel­oped ­with ­unique fea­tures, includ­ing ter­mi­nal remov­able pep­tide sig­nals direct­ing inter­nal­isa­tion of the ­decoy mole­cules to select­ed tar­get ­cells and nucle­ar local­iza­tion. These engi­neered mole­cules ­could be of ­great inter­est in in ­vivo experi­ments for devel­op­ment of treat­ment of ­human dis­eas­es asso­ciat­ed ­with NF-kB acti­va­tion, includ­ing sev­er­al inflam­ma­to­ry dis­eas­es.