Formation and structure of a novel enediyne-RNA base covalent adduct

Zhi Hong Jiang; Geum Sook Hwang; Zhen Xi; Irving H. Goldberg

doi:10.1021/ja0176292

Formation and structure of a novel enediyne-RNA base covalent adduct

Zhi Hong Jiang, Geum Sook Hwang, Zhen Xi, Irving H. Goldberg^*

^*Corresponding author for this work

School of Chinese Medicine

Research output: Contribution to journal › Journal article › peer-review

14 Citations (Scopus)

Abstract

The structure of an unusual covalent adduct formed by thiol-activated neocarzinostatin chromophore (NCS-chrom) and a RNA-DNA hybrid having an overhang of four unpaired residues at the 3-end of the RNA strand has been elucidated by MS and NMR spectroscopic analyses. Unlike previously characterized adducts formed by NCS-chrom on the sugar residue of the DNA target, this adduct has been found to be on one of the uracil bases in the RNA overhang. Covalent linkage is between C-6 of the post-activated NCS-chrom and C-5 of the uracil. A novel mechanism involving adduction of the NCS-chrom C-6 radical, generated by 2-mercaptoethanol activation, to C-5 of the uracil at the U9 position of the RNA 11-mer, oxidation by dioxygen, reduction by the thiol, and subsequent dehydration is proposed for adduct formation.

Original language	English
Pages (from-to)	3216-3217
Number of pages	2
Journal	Journal of the American Chemical Society
Volume	124
Issue number	13
DOIs	https://doi.org/10.1021/ja0176292
Publication status	Published - 3 Apr 2002

Scopus Subject Areas

Catalysis
General Chemistry
Biochemistry
Colloid and Surface Chemistry

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title = "Formation and structure of a novel enediyne-RNA base covalent adduct",

abstract = "The structure of an unusual covalent adduct formed by thiol-activated neocarzinostatin chromophore (NCS-chrom) and a RNA-DNA hybrid having an overhang of four unpaired residues at the 3-end of the RNA strand has been elucidated by MS and NMR spectroscopic analyses. Unlike previously characterized adducts formed by NCS-chrom on the sugar residue of the DNA target, this adduct has been found to be on one of the uracil bases in the RNA overhang. Covalent linkage is between C-6 of the post-activated NCS-chrom and C-5 of the uracil. A novel mechanism involving adduction of the NCS-chrom C-6 radical, generated by 2-mercaptoethanol activation, to C-5 of the uracil at the U9 position of the RNA 11-mer, oxidation by dioxygen, reduction by the thiol, and subsequent dehydration is proposed for adduct formation.",

author = "Jiang, {Zhi Hong} and Hwang, {Geum Sook} and Zhen Xi and Goldberg, {Irving H.}",

note = "This work was supported by Grant GM 53793 from the National Institutes of Health. G.-S.H. was supported by the Korea Science and Engineering Foundation. ",

year = "2002",

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doi = "10.1021/ja0176292",

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T1 - Formation and structure of a novel enediyne-RNA base covalent adduct

AU - Jiang, Zhi Hong

AU - Hwang, Geum Sook

AU - Xi, Zhen

AU - Goldberg, Irving H.

N1 - This work was supported by Grant GM 53793 from the National Institutes of Health. G.-S.H. was supported by the Korea Science and Engineering Foundation.

PY - 2002/4/3

Y1 - 2002/4/3

N2 - The structure of an unusual covalent adduct formed by thiol-activated neocarzinostatin chromophore (NCS-chrom) and a RNA-DNA hybrid having an overhang of four unpaired residues at the 3-end of the RNA strand has been elucidated by MS and NMR spectroscopic analyses. Unlike previously characterized adducts formed by NCS-chrom on the sugar residue of the DNA target, this adduct has been found to be on one of the uracil bases in the RNA overhang. Covalent linkage is between C-6 of the post-activated NCS-chrom and C-5 of the uracil. A novel mechanism involving adduction of the NCS-chrom C-6 radical, generated by 2-mercaptoethanol activation, to C-5 of the uracil at the U9 position of the RNA 11-mer, oxidation by dioxygen, reduction by the thiol, and subsequent dehydration is proposed for adduct formation.

AB - The structure of an unusual covalent adduct formed by thiol-activated neocarzinostatin chromophore (NCS-chrom) and a RNA-DNA hybrid having an overhang of four unpaired residues at the 3-end of the RNA strand has been elucidated by MS and NMR spectroscopic analyses. Unlike previously characterized adducts formed by NCS-chrom on the sugar residue of the DNA target, this adduct has been found to be on one of the uracil bases in the RNA overhang. Covalent linkage is between C-6 of the post-activated NCS-chrom and C-5 of the uracil. A novel mechanism involving adduction of the NCS-chrom C-6 radical, generated by 2-mercaptoethanol activation, to C-5 of the uracil at the U9 position of the RNA 11-mer, oxidation by dioxygen, reduction by the thiol, and subsequent dehydration is proposed for adduct formation.

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DO - 10.1021/ja0176292

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EP - 3217

JO - Journal of the American Chemical Society

JF - Journal of the American Chemical Society

IS - 13

ER -

Formation and structure of a novel enediyne-RNA base covalent adduct

Abstract

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