Structural characterization of formaldehyde-induced cross-links between amino acids and deoxynucleosides and their oligomers.
Structural characterization of formaldehyde-induced cross-links between amino acids and deoxynucleosides and their oligomers.
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DOI：
10.1021/ja908282f
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发表时间：
2010-03-17
影响因子：
15
通讯作者：
Swenberg, James A.
中科院分区：
文献类型：
--
作者：
Lu, Kun;Ye, Wenjie;Zhou, Li;Collins, Leonard B.;Chen, Xian;Gold, Avram;Ball, Louise M.;Swenberg, James A.
暴露于甲醛导致DNA-蛋白质交联（DPC）的形成，这是一种主要的遗传毒性效应。虽然DPC在生物学上很重要，并且已经报道了八种氨基酸与甲醛形成稳定的加合物，但这些交联的结构尚未阐明。我们的特点是甲酰亚胺诱导的交联的赖氨酸，半胱氨酸，组氨酸和色氨酸与dG，dA和dC。dT不形成交联，Arg、Gln、Tyr或Asn也不形成交联。甲醛与赖氨酸和dG反应得到的交联产物产率最高，其次是与半胱氨酸和dG反应。其他偶联反应的产率低10倍或更多。通过NMR和质谱法的详细结构检查确定氨基酸和单个核苷之间的交联涉及甲酰胺衍生的亚甲基桥。赖氨酸与dG产生了两个额外的产物，其中连接结构是1，N2-稠合的三嗪环。赖氨酸交联产物在室温下不稳定。反应性Nα-Boc保护的氨基酸与三核苷酸d（T1 B2 T3）之间的反应，其中B2是靶碱基G、A或C，以及dG，dA和dC以及在位置5处含有单个反应性靶残基的8-mer肽产生交联产物，其结构由高分辨率质谱推断，并且裂解模式与Nα-Boc-通过NMR研究严格测定保护的氨基酸和单核苷酸。这些结构将为研究体内形成的DPC的特征和性质提供基础，并将有助于鉴定用于评价接触部位和远处甲醛暴露的生物标志物。
Exposure to formaldehyde results in the formation of DNA-protein cross-links (DPCs) as a primary genotoxic effect. Although DPCs are biologically important and eight amino acids have been reported to form stable adducts with formaldehyde, the structures of these cross-links have not yet been elucidated. We have characterized formaldehyde-induced cross-links of Lys, Cys, His and Trp with dG, dA and dC. dT formed no cross-links, nor did Arg, Gln, Tyr or Asn. Reaction of formaldehyde with Lys and dG gave the highest yield of cross-linked products, followed by reaction with Cys and dG. Yields from the other coupling reactions were lower by a factor of 10 or more. Detailed structural examination by NMR and mass spectrometry established that the cross-links between amino acids and single nucleosides involve a formaldehyde-derived methylene bridge. Lys yielded two additional products with dG in which the linking structure is a 1,N2-fused triazino ring. The Lys cross-linked products were unstable at ambient temperature. Reactions between the reactive Nα-Boc-protected amino acids and the trinucleotides d(T1B2T3) where B2 is the target base G, A or C and reactions between dG, dA and dC and 8-mer peptides containing a single reactive target residue at position 5 yielded cross-linked products with structures inferred from high resolution mass spectrometry and fragmentation patterns that are consistent with those between Nα-Boc-protected amino acids and single nucleotides rigorously determined by NMR studies. These structures will provide a basis for investigation of the characteristics and properties of DPCs formed in vivo and will be helpful in identifying biomarkers for the evaluation of formaldehyde exposure both at site of contact and at distant sites.
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影响因子：
16.8
作者：
Daniels, DS;Woo, TT;Tainer, JA
通讯作者：
Tainer, JA
影响因子：
2.9
作者：
MCGHEE, JD;VONHIPPEL, PH
通讯作者：
VONHIPPEL, PH
影响因子：
2.7
作者：
Speit, G;Schütz, P;Merk, O
通讯作者：
Merk, O
DOI：
10.1016/0005-2787(73)90415-2
发表时间：
1973-01-01
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
SIOMIN, YA;SIMONOV, VV;POVERENN.AM
通讯作者：
POVERENN.AM
影响因子：
2.9
作者：
MCGHEE, JD;HIPPEL, PHV
通讯作者：
HIPPEL, PHV