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876 Nucleic Acid Synthesis

in anti-sense applications because of their enhanced sta- efficient uptake of PNA by living cells and the lack of
bility. The modified backbone of an S-oligo is resistant to efficient delivery systems.
the action of most nucleases and endonucleases, but they
also tend to be subject to more nonspecific interactions
due to “stickiness.” SEE ALSO THE FOLLOWING ARTICLES
BIOCONJUGATE CHEMISTRY • DNA TESTING IN FOREN-
A. Peptide Nucleic Acids (PNA) SIC SCIENCE • FIBER-OPTIC CHEMICAL SENSORS • GENE
EXPRESSION,REGULATION OF • HYBRIDOMAS,GENETIC
Peptide nucleic acids (PNA; Fig. 10) are synthetic polynu-
ENGINEERING OF • ION TRANSPORT ACROSS BIOLOGI-
cleobase molecules which bind to DNA and RNA with
CAL MEMBRANES • PROTEIN FOLDING • PROTEIN STRUC-
high affinity and specificity. PNA was constructed with
a charge-neutral, achiral, pseudopeptide backbone and is TURE • PROTEIN SYNTHESIS • TRANSLATION OF RNA TO
therefore chemically more closely related to peptides than PROTEIN
to nucleic acids. Thus, PNAs, because of their backbone
properties, show extremely good nucleic acid hybridiza-
tion properties. In fact, PNA–DNA and PNA–RNA du- BIBLIOGRAPHY
plexes are, in general, thermally more stable than the cor-
Eckstein, F. (2000). “Phosphorothioate oligodeoxynucleotides: What is
responding DNA(RNA)–DNA(RNA) duplexes.
their origin and what is unique about them?” Antisense Nucl. Acid
PNAsarerelativelyeasytosynthesizeandarestable(es-
Drug Dev. 10, 117–121.
pecially biologically). These make PNA an attractive can- Efimov, V. A., Buryakova, A. A., and Chakhmakhcheva, O. G. (1999).
didate for developing effective anti-sense and anti-gene “Synthesis of polyacrylamides N-substituted with PNA-like oligonu-
reagents and drugs. PNAs have been found to inhibit RNA cleotide mimics for molecular diagnostic applications,” Nucl. Acids
Res. 27, 4416–4426.
polymerase,humantelomerase,HIVreversetranscriptase,
Kornberg, A., and Baker, T. A. (1992). “DNA Replication,” Freeman,
and many more. Such PNAs are candidates for anti-cancer
New York.
drugs and also as a means of developing novel drugs to Lewin, B. (2000). “Genes VII,” Oxford Univ. Press, New York.
treat HIV infections (AIDS). Despite these encouraging Malik, S., and Roeder, R. G. (2000). “Transcriptional regulation through
results, further progress is very much impeded by the in- mediator-like coactivators in yeast and metazoan cells,” Trends
Biochem. Sci. 25, 277–283.
Mooney, R. A., Artsimovitch, I., and Landick, R. (1998). “Information
processing by RNA polymerase: Recognition of regulatory signals
during RNA chain elongation,” J. Bacteriol. 180, 3265–3275.
Nielsen, P. E. (2000). “Peptide nucleic acids: On the road to new gene
therapeutic drugs,” Pharmacol. Toxicol. 86, 3–7.
Peterson, C. L., and Logie, C. (2000). “Recruitment of chromatin re-
modeling machines,” J. Cell. Biochem. 78, 179–185.
Ray, A., and Norden, B. (2000). “Peptide nucleic acid (PNA): Its medical
and biotechnical applications and promise for the future,” FASEB J.
14, 1041–1060.
Stuart, K., Allen, T. E., Heidmann, S., and Seiwert, S. D. (1997). “RNA
editing in kinetoplastid protozoa,” Microbiol. Mol. Biol. Rev. 61, 105–
120.
Sudarsanam, P., and Winston, F. (2000). “The Swi/Snf family—
nucleosome-remodeling complexes and transcriptional control,”
Trends Genet. 16, 345–351.
Summers, D. K. (1996). “The Biology of Plasmids,” pp. 39–62, Black-
FIGURE 10 Structure of peptide nucleic acid (PNA). An artificial well Sci., Oxford.
oligomer produced by chemical synthesis retains the ability to pair Uhlmann, E. (1998). “Peptide nucleic acids (PNA) and PNA-DNA
with bases, but is resistant to degradation by nucleases because chimeras: From high binding affinity towards biological function,”
its backbone does not contain the normal phosphodiester linkage. Biol. Chem. 379, 1045–1052.