TETRAHEDRON
LETTERS
Tetrahedron Letters 42 (2001) 5733–5735 Pergamon
Photochemical cleavage of single- and double-stranded
oligonucleotides by 3-(p -tolylamino)-1,5-azulenequinone
Fu-Yuan Tsai,
a,b
Shwu-Bin Lin,
c
Shwu-Chen Tsay,
a
Wei-Chen Lin,
a
Chia-Lin Hsieh,
d
Shih Hsien Chuang,
b
Lou-Sing Kan
a,d,
* and Jih Ru Hwu
a,b,
*
a
Institute of Chemistry, Academia Sinica, Taipei 11529, Taiwan
b
Department of Chemistry, National Tsing Hua University, Hsinchu 30043, Taiwan
c
The Graduate Institute of Medical Technology, National Taiwan University, Taipei, Taiwan
d
Institute of Biochemistry, National Chung -Hsing University, Taichung, China (Taiwan)
Received 7 February 2001; accepted 1 June 2001
Abstract—Irradiation, with 350 nm UV light, of specially designed and synthesized single- and double-stranded oligodeoxyribo-
nucleotides in the presence of 3-(p -tolylamino)-1,5-azulenequinone produced fragments resulting from the cleavage at the
deoxyguanosine residue only. The cleaving efficiency was greater for a single strand than a double helix. The efficiency was
increased for a less stable double helix, or while the deoxyguanosine residue therein was located at a bulge, at a hairpin loop, or
towards the end of the helix. © 2001 Elsevier Science Ltd. All rights reserved.
Most quinones are benzoquinones or polybenzenoid
hydrocarbons.
1
Azulenequinones are non-benzenoid;
some of these cytotoxic compounds have been tested
against P-388 leukemia in mice.
1
Upon activation by
UV light,
2
many azulenequinones exhibit DNA-cleav-
ing activity under controlled conditions.
3
3-(p -Tolyl-
amino)-1,5-azulenequinone 1 represents a prominent
example; it exhibits great potency and site-specificity
for the deoxyguanosine residue.
3,4
We planned to study
the interactions between this organic compound and
various oligodeoxyribonucleotides. The results would
provide valuable information about the influences
resulting from secondary structure on the reaction
between deoxyguanosine and azulenequinones during
DNA cleavage.
A series of duplexes with different features were
designed as listed in Table 1. Each duplex in entries 1,
2 and 4 contains 15 nucleotidyl units, among which
there are 14 adenine:thymine (A:T) base pairs. The S1
and S2 oligodeoxyribonucleotides possess only one gua-
nine (G) nucleoside, which is located either in the
middle (i.e. S1) or near the 3-end (i.e. S2). Further-
more, we designed their complementary sequences in
the C-series by forming the Watson–Crick base pairs.
In entry 3, A15 contains 15-adenyl units, whereas its
Table 1. The sequences of oligodeoxyribonucleotides containing a deoxyguanosine, their complementary oligomers, and the
melting temperature (T
m
) of the corresponding duplexes (20 mM) in a tris buffer solution with pH 7.0 containing 0.15 M
NaCl and 20 mM MgCl
2
Description Complementary oligomer Oligonucleotide Entry T
m
(°C)
5-T
7
GT
7
(S1) 1 5-A
7
CA
7
(C1) Watson–Crick 48
5-T
13
GT (S2) 5-ACA
13
(C2) Watson–Crick 48 2
5-T
7
GT
8
(S1T) 5-A
15
(A15) Bulge 39 3
39 One mismatch 5-A
15
(A15) 4 5-T
7
GT
7
(S1)
51 5 5-(AT)
4
TGT(AT)
4
(H3) Hairpin
49 Hairpin 6 5-(AT)
4
TTGTT(AT)
4
(H5)
Keywords : azulenequinone; DNA cleavage; deoxyguanosine; site-specificity; photochemistry.
* Corresponding author. Fax: +886-22-788-1337; e-mail: jrhwu@chem.sinica.edu.tw
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
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