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  APPLICATIONS OF PEPTIDES NUCLEIC ACIDS (PNA) IN MOLECULAR MEDICINE AND BIOTECHNOLOGYFREEfree


Minerva Biotecnologica 1999 September;11(3):205-10

Copyright © 1999 EDIZIONI MINERVA MEDICA

lingua: Inglese

Effects of peptide nucleic acids (PNAs) on gene transcription

Mischiati C. 1, Rutigliano C. 1, Feriotto G. 1, 2, Borgatti M. 1, Bianchi N. 1, Gambari R. 2

1 Department of Biochemistry and Molecular Biology, Ferrara University, Ferrara, Italy; 2 Biotechnology Centre, Ferrara University, Ferrara, Italy


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Pep­tide ­nucleic ­acids (­PNAs) ­have ­recently ­been pro­posed as ­useful ­reagents in experi­ments ­aimed at the con­trol of ­gene expres­sion. ­PNAs back­bone con­sists of N-(2-ami­no­ethyl)-gly­cine ­units ­linked by ­amide ­bonds; there­fore, ­these mole­cules are ach­iral and neu­tral, and are ­extremely effi­cient in hybri­dizing ­with DNA and RNA, gen­er­ating PNA-DNA and PNA-RNA ­hybrid mole­cules exhib­iting ­high ­stability ­even at low and ­medium ­ionic ­strength. PNA-medi­ated ­effects on in ­vitro and ex ­vivo tran­scrip­tion are ­here ­reviewed. ­Enhancing or inhib­i­tory ­activity of ­PNAs on ­gene tran­scrip­tion ­have ­been ­reported to be ­mainly due to a pro­cess ­which ­involves ­strand inva­sion of ­target DNA con­taining homo­pu­rine/homo­py­ri­mid­i­ne s­tretches ­with the gen­er­a­tion of (PNA)2/DNA trip­lexes. On the con­trary, few infor­ma­tions are avail­able on the pos­sible use of ­PNAs as “decoy” mole­cules ­able to ­interact ­with DNA-­binding pro­teins, ­including tran­scrip­tion fac­tors. In ­this ­paper we ­also ­reviewed ­results ­from our labor­a­tory ­obtained stud­ying the ­effects of DNA/DNA, DNA/PNA or PNA/PNA mole­cules mim­icking the NF-kB ­binding ­sites of the ­human immu­no­def­i­ciency ­type 1 ­virus (HIV-1) on ­long ter­minal ­repeat (LTR)-­driven in ­vitro tran­scrip­tion. The ­results ­herein ­reported ­allow to sug­gest ­that PNA/PNA mole­cules and DNA/PNA ­hybrids are ­capable to ­inhibit tran­scrip­tion ­through dif­ferent mech­a­nisms of ­action. The ­effects of ­PNAs and PNA/PNA ­hybrids on tran­scrip­tion are ­mainly due to ­strand inva­sion of ­target ­gene ­sequences. On the con­trary, the ­activity of DNA/PNA on in ­vitro ­gene tran­scrip­tion ­could be due to ­direct inter­ac­tion ­with tran­scrip­tion fac­tors. ­These ­results ­should ­encourage ­studies on mod­i­fied ­PNAs in ­order to deter­mine ­whether ­PNAs ­could be ­designed, syn­the­tized and ­tested to ­exhibit a ­sequence-spe­cific “­decoy” ­activity. For ­this ­point of ­view, ­chiral ­PNAs, ­PHONA (in ­which the pep­tide ­bond is ­replaced by a phos­phonic ­acid ­ester ­bridge) and PNA-DNA chi­meras ­should be con­sid­ered as poten­tial mole­cules ­able to dis­play effi­cient ­sequence-spe­cific inter­ac­tions ­with ­target pro­teins.

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