Home > Riviste > Minerva Biotecnologica > Fascicoli precedenti > Minerva Biotecnologica 1999 September;11(3) > Minerva Biotecnologica 1999 September;11(3):205-10

ULTIMO FASCICOLO
 

JOURNAL TOOLS

eTOC
Per abbonarsi PROMO
Sottometti un articolo
Segnala alla tua biblioteca
 

ARTICLE TOOLS

Estratti
Permessi

 

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

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


PDF


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.

inizio pagina