TY - JOUR
T1 - Chemistry of the Alkali-Labile Lesion Formed from Iron(II) Bleomycin and d(CGCTTTAAAGCG)
AU - Sugiyama, Hiroshi
AU - Xu, Cheng
AU - Murugesan, Natesan
AU - Hecht, Sidney M.
AU - Van Boom, Jacques H.
AU - Van Der Marel, Gijs A.
PY - 1988/1/1
Y1 - 1988/1/1
N2 - Two sets of products are formed from DNA upon treatment with Fe(II)·bleomycin + O2. One set, which is believed to derive from a C-4’ hydroperoxy derivative of the DNA deoxyribose moiety, includes the four possible base propenals, as well as DNA oligomers having deoxynucleoside 3’-(phosphoro-2“-O-glycolates) at their 3’-termini. The other set of products consists of free bases and alkali-labile lesions, the latter of which had not previously been characterized structurally. By use of the self-complementary dodecanucleotide d(CGCTTTAAAGCG) having a site modified by Fe•bleomycin three nucleotides from the 5’-end, it has been possible to characterize the alkali-labile product as a C-4’ hydroxyapurinic acid. When the bleomycin-treated dodecanucleotide was treated with agents that effected decomposition of the alkali-labile lesion, products of the form CpGpx were obtained, and these proved useful for structural characterization of the alkali-labile lesion. Treatment with alkali produced CpGpx, where x was 2,4-dihydroxycyclopentenone. Alternatively, treatment with hydrazine provided a pyridazine derivative, and aqueous alkylamines led to formation of CpGp itself. The structures of all dinucleotides produced from the alkali-labile lesion were verified by direct comparison with authentic synthetic samples.
AB - Two sets of products are formed from DNA upon treatment with Fe(II)·bleomycin + O2. One set, which is believed to derive from a C-4’ hydroperoxy derivative of the DNA deoxyribose moiety, includes the four possible base propenals, as well as DNA oligomers having deoxynucleoside 3’-(phosphoro-2“-O-glycolates) at their 3’-termini. The other set of products consists of free bases and alkali-labile lesions, the latter of which had not previously been characterized structurally. By use of the self-complementary dodecanucleotide d(CGCTTTAAAGCG) having a site modified by Fe•bleomycin three nucleotides from the 5’-end, it has been possible to characterize the alkali-labile product as a C-4’ hydroxyapurinic acid. When the bleomycin-treated dodecanucleotide was treated with agents that effected decomposition of the alkali-labile lesion, products of the form CpGpx were obtained, and these proved useful for structural characterization of the alkali-labile lesion. Treatment with alkali produced CpGpx, where x was 2,4-dihydroxycyclopentenone. Alternatively, treatment with hydrazine provided a pyridazine derivative, and aqueous alkylamines led to formation of CpGp itself. The structures of all dinucleotides produced from the alkali-labile lesion were verified by direct comparison with authentic synthetic samples.
UR - http://www.scopus.com/inward/record.url?scp=0023829779&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0023829779&partnerID=8YFLogxK
U2 - 10.1021/bi00401a011
DO - 10.1021/bi00401a011
M3 - Article
C2 - 2450572
AN - SCOPUS:0023829779
SN - 0006-2960
VL - 27
SP - 58
EP - 67
JO - Biochemistry
JF - Biochemistry
IS - 1
ER -