ORGANIC
LETTERS
2001
Vol. 3, No. 6
925-927
Synthesis and Properties of Peptide
Nucleic Acids Containing a Psoralen
Unit
Akimitsu Okamoto, Kazuhito Tanabe, and Isao Saito*
Department of Synthetic Chemistry and Biological Chemistry, Faculty of Engineering,
Kyoto UniVersity, CREST, Japan Science and Technology Corporation (JST),
Kyoto 606-8501, Japan
Received January 11, 2001
ABSTRACT
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We prepared the psoralen PNA unit from 8-methoxypsoralen and synthesized various PNAs containing psoralen by a typical Boc method.
PNAs containing psoralen (P-PNA) at strand end formed a stable duplex with complementary DNA. The hybridization of P-PNA with complementary
DNA resulted in a considerable decrease of the psoralen fluorescence.
Studies on the molecular basis for photosensitization induced
by psoralen derivatives have attracted considerable attention
in recent years.1 These include investigations of the lumi-
nescence properties of their excited states,2 the formation of
psoralen-pyrimidine base cross-link via [2 + 2]photo-
cycloaddition,3 cell killing,4 and the cure of skin diseases
such as psoriasis.5 Psoralens exhibit strong fluorescence by
UVA irradiation, and the labeling of DNA and RNA by
psoralen is been a promising tool for monitoring interactions
with other biomolecules.6
recognize a complementary DNA sequence in a highly
sequence-specific manner.7 The PNA-DNA hybrid is ther-
modynamically more stable than DNA duplex,8 and it is
fairly independent of ionic strength in solutions.9 Moreover,
the incorporation of modified nucleobases into PNA is
relatively easy. Therefore, incorporation of a psoralen unit
into PNA seems to be very attractive. The sequence-specific
DNA recognition by psoralen-containing PNA would po-
tentially be used for the readout of a DNA sequence by
monitoring characteristic psoralen fluorescence.
Peptide nucleic acid (PNA) is a completely artificial
nucleic acid consisting of a peptide backbone. PNA can
Herein we report the synthesis and properties of PNAs
containing psoralen (P-PNA). We synthesized the psoralen
t
(1) Cimino, G. D.; Gamper, H. B.; Isaacs, S. T.; Hearst, J. E. Annu.
ReV. Biochem. 1985, 54, 1151-1193.
PNA unit and then incorporated it into PNA by the BOC
method. The fluorescence of P-PNA considerably decreased
upon forming a PNA-DNA hybrid.
(2) Seret, A.; Piette, J.; Jakobs, A.; Vandevorst, A. Photochem. Photobiol.
1992, 56, 409-412.
(3) For a review, see: Thuong, N. T.; He´le`ne, C. Angew. Chem., Int.
Ed. Engl. 1993, 32, 666-690.
(4) (a) Csik, G.; Ronto, G.; Nocentini, S. J. Photochem. Photobiol. B
1994, 24, 129-139. (b) Misra, R. R.; Vos, J. M. H. Mol. Cell. Biol. 1993,
13, 1002-1012.
(6) Lai, T.; Lim, B. T.; Lim, E. C. J. Am. Chem. Soc. 1982, 104, 7631-
7635.
(7) Nielsen, P. Acc. Chem. Res. 1999, 32, 624-630.
(8) (a) Schwarz, F. P.; Robinson, S.; Butler, J. M. Nucleic Acids Res.
1999, 27, 4792-4800. (b) Chakrabarti, M. C.; Schwarz, F. P. Nucleic Acids
Res. 1999, 27, 4801-4806.
(9) Tomac, S.; Sarkar, M.; Ratilainen, T.; Wittung, P.; Nielsen, P. E.;
Norde´n, B.; Gra¨slund, A. J. Am. Chem. Soc. 1996, 118, 5544-5552.
(5) (a) Johnson, R.; Staiano-Coico, L.; Austin, L.; Cardinale, I.; Nabeya-
Tsukifuji, R.; Krueger, J. G. Photochem. Photobiol. 1996, 63, 566-571.
(b) Dall’Acqua, F.; Vedaldi, D. In Handbook of Organic Photochemistry
and Photo biology; Horspool, W. M., Song, P.-S., Eds.; CRC Press: Boca
Raton, FL, 1995; pp 1357-1366.
10.1021/ol015549x CCC: $20.00 © 2001 American Chemical Society
Published on Web 02/27/2001