Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET

User menu

  • My alerts
  • Log in
  • My Cart

Search

  • Advanced search
Molecular Pharmacology
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET
  • My alerts
  • Log in
  • My Cart
Molecular Pharmacology

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Visit molpharm on Facebook
  • Follow molpharm on Twitter
  • Follow molpharm on LinkedIn
Abstract

A theoretical study of the comparative binding affinities of daunomycin derivatives to a double-stranded oligomeric DNA. Proposal for new high affinity derivatives.

K X Chen, N Gresh and B Pullman
Molecular Pharmacology September 1986, 30 (3) 279-286;
K X Chen
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
N Gresh
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
B Pullman
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Info & Metrics
  • eLetters
  • PDF
Loading

Abstract

Theoretical computations were performed on the comparative binding affinities of daunomycin (DM, 1) and seven derivatives related to the double-stranded oligonucleotide d(CGATCG)2. The compounds investigated were 4-demethoxy DM (2), and its beta-anomer (3), 4-demethoxy-7,9-bis-epi DM (4) and its beta anomer (5), a derivative with glucosamine instead of daunosamine (6), and two additional hypothetical DM derivatives in which the cationic NH3+ group of the daunosamine moiety is replaced by either a CH2--NH3+ group (7) or a CH2CH2NH3+ group (8), so as to indicate the effect on the binding affinity of interposing one- or two-methylene groups between the sugar and the cationic charge. The conformational angles of the hexanucleotide are fixed in values found in the representative crystal structure of the d(CGTACG)2-DM complex. The intermolecular drug-hexanucleotide interaction energies and the conformational energy changes of the drug upon binding are computed and optimized in the framework of the SIBFA procedure (sum of interactions between fragments computed ab initio), which uses empirical formulas based on ab initio SCF computations. The overall binding affinity ordering of compounds 1-6 compares satisfactorily with the ordering of available experimental affinity constants. The binding affinities of compounds 7 and 8, for which no experimental results seem to be available yet, are predicted to be significantly higher than those of the parent compound DM, with the greatest affinity found for 7. Because of the overall correlation between binding affinity of anthracyclines to DNA and their antitumor activity, these last two compounds deserve an exploration of their chemotherapeutic efficiency.

MolPharm articles become freely available 12 months after publication, and remain freely available for 5 years. 

Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page. 

 

  • Click here for information on institutional subscriptions.
  • Click here for information on individual ASPET membership.

 

Log in using your username and password

Forgot your user name or password?

Purchase access

You may purchase access to this article. This will require you to create an account if you don't already have one.
PreviousNext
Back to top

In this issue

Molecular Pharmacology
Vol. 30, Issue 3
1 Sep 1986
  • Table of Contents
  • Table of Contents (PDF)
  • Index by author
  • Back Matter (PDF)
  • Editorial Board (PDF)
  • Front Matter (PDF)
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Molecular Pharmacology article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
A theoretical study of the comparative binding affinities of daunomycin derivatives to a double-stranded oligomeric DNA. Proposal for new high affinity derivatives.
(Your Name) has forwarded a page to you from Molecular Pharmacology
(Your Name) thought you would be interested in this article in Molecular Pharmacology.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Abstract

A theoretical study of the comparative binding affinities of daunomycin derivatives to a double-stranded oligomeric DNA. Proposal for new high affinity derivatives.

K X Chen, N Gresh and B Pullman
Molecular Pharmacology September 1, 1986, 30 (3) 279-286;

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero

Share
Abstract

A theoretical study of the comparative binding affinities of daunomycin derivatives to a double-stranded oligomeric DNA. Proposal for new high affinity derivatives.

K X Chen, N Gresh and B Pullman
Molecular Pharmacology September 1, 1986, 30 (3) 279-286;
del.icio.us logo Digg logo Reddit logo Twitter logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

Similar Articles

Advertisement
  • Home
  • Alerts
Facebook   Twitter   LinkedIn   RSS

Navigate

  • Current Issue
  • Fast Forward by date
  • Fast Forward by section
  • Latest Articles
  • Archive
  • Search for Articles
  • Feedback
  • ASPET

More Information

  • About Molecular Pharmacology
  • Editorial Board
  • Instructions to Authors
  • Submit a Manuscript
  • Customized Alerts
  • RSS Feeds
  • Subscriptions
  • Permissions
  • Terms & Conditions of Use

ASPET's Other Journals

  • Drug Metabolism and Disposition
  • Journal of Pharmacology and Experimental Therapeutics
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-0111 (Online)

Copyright © 2022 by the American Society for Pharmacology and Experimental Therapeutics