This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.


277d

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 1: Line 1:
-
[[Image:277d.jpg|left|200px]]
+
{{Seed}}
 +
[[Image:277d.png|left|200px]]
<!--
<!--
Line 9: Line 10:
{{STRUCTURE_277d| PDB=277d | SCENE= }}
{{STRUCTURE_277d| PDB=277d | SCENE= }}
-
'''SUBSTITUTIONS AT C2' OF DAUNOSAMINE IN THE ANTICANCER DAUNORUBICIN ALTER ITS DNA-BINDING SEQUENCE SPECIFICITY'''
+
===SUBSTITUTIONS AT C2' OF DAUNOSAMINE IN THE ANTICANCER DAUNORUBICIN ALTER ITS DNA-BINDING SEQUENCE SPECIFICITY===
-
==Overview==
+
<!--
-
In the search for new generations of anthracycline drugs, lower cytotoxic side effect and higher activity toward resistant cancer cells are two major goals. A new anthracycline drug, WP401 (2'-bromo-4'-epidaunorubicin, alpha-manno configuration), exhibits promising activity toward multidrug-resistant cells. In contrast, the related compound WP400 (2'-bromo-4'-epidaunorubicin, alpha-gluco configuration), is significantly less cytotoxic. To establish the structural and molecular bases of this observation, we performed X-ray diffraction analyses of the complexes between WP401 and four DNA hexamers CGTACG, CGATCG, CGCGCG, and CGGCCG. Their crystal data (space group P4(1)2(1)2, a = b approximately 2.8 nm, c approximately 5.3 nm) are similar to those of other daunorubicin/doxorubicin complexes. The refined crystal structures at 0.18-nm resolution revealed that two WP401 drug molecules bind to the duplex, with the aglycons intercalated between the CpG steps and their modified daunosamines in the minor groove. The bulky bromine atom at the C2' position caused the daunosamine of the bound WP401 to adopt a different conformation from that of the bound daunorubicin. In the presence of formaldehyde, WP401 formed a covalent adduct with CGGCCG more readily than with CGCGCG. This is the opposite of what is seen for daunorubicin and doxorubicin. Thus modifications at the C2' position of daunosamine modulate the sequence specificity of the formaldehyde-crosslinking reactions between anthracyclines and DNA.
+
The line below this paragraph, {{ABSTRACT_PUBMED_8841395}}, adds the Publication Abstract to the page
 +
(as it appears on PubMed at http://www.pubmed.gov), where 8841395 is the PubMed ID number.
 +
-->
 +
{{ABSTRACT_PUBMED_8841395}}
==About this Structure==
==About this Structure==
Line 27: Line 31:
[[Category: Modified]]
[[Category: Modified]]
[[Category: Right handed dna]]
[[Category: Right handed dna]]
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 18:25:07 2008''
+
 
 +
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 00:40:10 2008''

Revision as of 21:40, 27 July 2008

Image:277d.png

Template:STRUCTURE 277d

SUBSTITUTIONS AT C2' OF DAUNOSAMINE IN THE ANTICANCER DAUNORUBICIN ALTER ITS DNA-BINDING SEQUENCE SPECIFICITY

Template:ABSTRACT PUBMED 8841395

About this Structure

Full crystallographic information is available from OCA.

Reference

Substitutions at C2' of daunosamine in the anticancer drug daunorubicin alter its DNA-binding sequence specificity., Gao YG, Priebe W, Wang AH, Eur J Biochem. 1996 Sep 1;240(2):331-5. PMID:8841395

Page seeded by OCA on Mon Jul 28 00:40:10 2008

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/277d"
Personal tools