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Impact of biophysical parameters on the biological assessment of peptide nucleic acids, antisense inhibitors of gene expression
Author(s) -
Noble Stewart A.,
Bonham Michele A.,
Bisi John E.,
Bruckenstein David A.,
Brown Pamela H.,
Brown Stephen C.,
Cadilla Rodolfo,
Gaul Micheal D.,
Hanvey Jeffery C.,
Fred Hassman C.,
Josey John A.,
Luzzio Michael J.,
Myers Philip M.,
Pipe Adrian J.,
Ricca Daniel J.,
Su Charles W.,
Stevenson Cynthia L.,
Thomson Stephen A.,
Wiethe Robert W.,
Babiss Lee E.
Publication year - 1995
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.430340208
Subject(s) - nucleic acid , rna , biochemistry , dna , chemistry , oligonucleotide , gene expression , microbiology and biotechnology , sense (electronics) , biology , gene
Peptide nucleic acids (PNA) are oligodeoxynucleotide (ODN) analogs in which the sugar phosphate backbone of the ODN has been replaced by one derived from units of N‐ethylaminoglycine. PNAs recognize DNA and RNA in a sequence specific manner and form complexes that can be characterized by biophysical methods. The binding motif is context dependent; homopyrimidine PNAs combine with complementary polypurine targets to form stoichiometric 2:1 complexes, whereas PNAs containing both purine and pyrimidine bases afford a 1:1 heteroduplex with mis‐match sensitivity comparable to that found in dsDNA. These complexes mediate the antigene and antisense effects of PNAs via the steric blockade of enzyme complexes responsible for DNA transcription, cDNA synthesis, and RNA translation. PNAs, like ODNs, are taken up by cells via endocytosis leading to their entrapment within intracytoplasmic vesicles. Under circumstances where agent delivery is solved by cell microinjection, PNAs can effect selective inhibition of endogenous and exogenous genes. The impact of biophysical parameters on the biological assessment of PNAs as antisense inhibitors of gene expression is presented and discussed. © 1995 Wiley‐Liss, Inc.