Identification of fluorescent 2 '-deoxyadenosine adducts formed in reactions of conjugates of malonaldehyde and acetaldehyde, and of malonaldehyde and formaldehyde
F. Le Curieux et al., Identification of fluorescent 2 '-deoxyadenosine adducts formed in reactions of conjugates of malonaldehyde and acetaldehyde, and of malonaldehyde and formaldehyde, CHEM RES T, 13(12), 2000, pp. 1228-1234
2'-Deoxyadenosine was reacted with malonaldehyde in the presence of formald
ehyde or acetaldehyde. The reactions were carried out at 37 degreesC in aqu
eous solution at acidic conditions. The reaction mixtures were analyzed by
HPLC. In both reactions, two major products were formed. The reaction produ
cts were isolated and purified by C18 chromatography, and their structures
were characterized by UV absorbance, fluorescence emission, H-1 and C-13 NM
R spectroscopy, and mass spectrometry. The reaction products isolated from
the mixture containing formaldehyde, malonaldehyde, and deoxyadenosine were
identified as beta-(2'-deoxy-beta -D-ribofuranosyl)-7H-8-formyl [2,1-i] py
rimidopurine (M(1)FA-dA) and 9-( 2'-deoxy-beta -D-ribofuranosyl)-6-(3,5-dif
ormyl-1,4-dihydro-1-pyrid (M(2)FA-dA). In the reaction mixture consisting o
f acetaldehyde, malonaldehyde, and deoxyadenosine, the identities of the pr
oducts were determined to be 3-(2'-deoxy-beta -D-ribofuranosyl)-7-methyl-8f
ormyl[2,1i]pyrimidopurine (M-1-AA-dA) and 9-(2'-deoxy-beta -D-ribofuranosyl
)-6-(3,5-di (M(2)AA-dA). The yields of the compounds were 1.8 and 0.7% for
M(1)FA-dA and M(2)FA-dA, respectiviely, and 6.8 and 10% for M(1)AA-dA and M
(2)AA-dA, respectively. AU compounds exhibited marked fluorescent propertie
s. These findings show that in addition to direct reaction of a specific al
dehyde with 2'-deoxyadenosine, aldehyde conjugates also may react with the
base. Although three of the adducts (M(1)FA-dA, M(2)FA-dA, and M(1)AA-dA) c
ould not be detected in reactions carried out under neutral conditions, the
possibility that trace anlounts of the adducts may be formed under physiol
ogical conditions cannot be ruled out. Therefore, conjugate adducts must be
considered in work that aims at clarifying the mechanism of aldehyde genot
oxicity.