1d33
From Proteopedia
(New page: 200px<br /><applet load="1d33" size="450" color="white" frame="true" align="right" spinBox="true" caption="1d33, resolution 1.500Å" /> '''FORMALDEHYDE CROSS-...) |
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| - | [[Image:1d33.gif|left|200px]]<br /><applet load="1d33" size=" | + | [[Image:1d33.gif|left|200px]]<br /><applet load="1d33" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1d33, resolution 1.500Å" /> | caption="1d33, resolution 1.500Å" /> | ||
'''FORMALDEHYDE CROSS-LINKS DAUNORUBICIN AND DNA EFFICIENTLY: HPLC AND X-RAY DIFFRACTION STUDIES'''<br /> | '''FORMALDEHYDE CROSS-LINKS DAUNORUBICIN AND DNA EFFICIENTLY: HPLC AND X-RAY DIFFRACTION STUDIES'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Formaldehyde (HCHO) cross-links the anticancer drug daunorubicin (DAU) to | + | Formaldehyde (HCHO) cross-links the anticancer drug daunorubicin (DAU) to DNA efficiently. When DAU is mixed with DNA hexamers, d(CGCGCG) and d(CGTDCG), in the presence of HCHO, stable covalent adducts of DNA are formed, as shown by the HPLC analyses. The major adducts are identical with the materials in the respective crystals which can be readily obtained from the 1:1 mixture of DAU-d(CGCGCG) and DAU-d(CGTDCG) plus HCHO, but not from the solution without HCHO. The high-resolution (1.5 A) X-ray crystal structure of those adducts shows unambiguously that they contain a covalent methylene bridge between the N3' of daunosamine and the N2 of the guanine or 2-aminoadenine. The perfect juxtaposition of the two amino groups in the minor groove of the complex provides a template for an efficient addition of HCHO. The methylene bridge does not perturb the conformation of the drug-DNA complex, when compared to the structure of DAU-d(CGTACG). The results suggest new approaches for synthesizing a new type of potential anticancer drug by attaching a reactive (e.g., alkylating) functional group at the N3' amino position of daunorubicin/doxorubicin. The stable drug-DNA adduct may be useful as probes for other biological studies. |
==About this Structure== | ==About this Structure== | ||
| - | 1D33 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ] with DM1 and MG as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 1D33 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ] with <scene name='pdbligand=DM1:'>DM1</scene> and <scene name='pdbligand=MG:'>MG</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1D33 OCA]. |
==Reference== | ==Reference== | ||
Formaldehyde cross-links daunorubicin and DNA efficiently: HPLC and X-ray diffraction studies., Wang AH, Gao YG, Liaw YC, Li YK, Biochemistry. 1991 Apr 23;30(16):3812-5. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=2018756 2018756] | Formaldehyde cross-links daunorubicin and DNA efficiently: HPLC and X-ray diffraction studies., Wang AH, Gao YG, Liaw YC, Li YK, Biochemistry. 1991 Apr 23;30(16):3812-5. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=2018756 2018756] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| - | [[Category: Gao, Y | + | [[Category: Gao, Y G.]] |
| - | [[Category: Li, Y | + | [[Category: Li, Y K.]] |
| - | [[Category: Liaw, Y | + | [[Category: Liaw, Y C.]] |
| - | [[Category: Wang, A | + | [[Category: Wang, A H.J.]] |
[[Category: DM1]] | [[Category: DM1]] | ||
[[Category: MG]] | [[Category: MG]] | ||
| Line 23: | Line 23: | ||
[[Category: right handed dna]] | [[Category: right handed dna]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:12:25 2008'' |
Revision as of 10:12, 21 February 2008
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FORMALDEHYDE CROSS-LINKS DAUNORUBICIN AND DNA EFFICIENTLY: HPLC AND X-RAY DIFFRACTION STUDIES
Overview
Formaldehyde (HCHO) cross-links the anticancer drug daunorubicin (DAU) to DNA efficiently. When DAU is mixed with DNA hexamers, d(CGCGCG) and d(CGTDCG), in the presence of HCHO, stable covalent adducts of DNA are formed, as shown by the HPLC analyses. The major adducts are identical with the materials in the respective crystals which can be readily obtained from the 1:1 mixture of DAU-d(CGCGCG) and DAU-d(CGTDCG) plus HCHO, but not from the solution without HCHO. The high-resolution (1.5 A) X-ray crystal structure of those adducts shows unambiguously that they contain a covalent methylene bridge between the N3' of daunosamine and the N2 of the guanine or 2-aminoadenine. The perfect juxtaposition of the two amino groups in the minor groove of the complex provides a template for an efficient addition of HCHO. The methylene bridge does not perturb the conformation of the drug-DNA complex, when compared to the structure of DAU-d(CGTACG). The results suggest new approaches for synthesizing a new type of potential anticancer drug by attaching a reactive (e.g., alkylating) functional group at the N3' amino position of daunorubicin/doxorubicin. The stable drug-DNA adduct may be useful as probes for other biological studies.
About this Structure
1D33 is a Protein complex structure of sequences from [1] with and as ligands. Full crystallographic information is available from OCA.
Reference
Formaldehyde cross-links daunorubicin and DNA efficiently: HPLC and X-ray diffraction studies., Wang AH, Gao YG, Liaw YC, Li YK, Biochemistry. 1991 Apr 23;30(16):3812-5. PMID:2018756
Page seeded by OCA on Thu Feb 21 12:12:25 2008
Categories: Protein complex | Gao, Y G. | Li, Y K. | Liaw, Y C. | Wang, A H.J. | DM1 | MG | Complexed with drug | Double helix | Modified | Right handed dna
