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

Template 2-chloro-2'-deoxyadenosine monophosphate inhibits in vitro DNA synthesis.

P Hentosh and P Grippo
Molecular Pharmacology May 1994, 45 (5) 955-961;
P Hentosh
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
P Grippo
  • 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

2'-Chloro-2'-deoxyadenosine triphosphate (cladribine), a purine nucleotide analog and potent antileukemic agent, was enzymatically incorporated into 98-base oligomers in place of dATP to investigate the molecular consequences of 2-chloroadenine (CIAde) in DNA. We have used the resultant oligomers as templates for purified DNA polymerases, to compare the rate and extent of in vitro DNA synthesis; the sites of polymerase pausing, if any; and the effects of increasing deoxyribonucleoside triphosphate (dNTP) concentrations on synthetic reactions. Compared with control template, CIAde-containing DNA strikingly reduced the overall amount and rate of chain elongation by human polymerase beta and Klenow fragment. Distinct pause sites, which were polymerase dependent, occurred primarily one or two bases before or just after nucleotide incorporation opposite template CIAde. Human polymerase alpha and phage T4 DNA polymerase likewise exhibited reduced synthesis on CIAde-substituted templates. Bypassing of CIAde residues was possible only at higher dNTP concentrations, with approximately 20- and 50-fold greater dNTP concentrations being required for synthesis beyond CIAde sites, compared with adenine residues, by polymerase alpha and beta, respectively. These results suggest that CiAde residues located within cellular template DNA may inhibit daughter strand synthesis and thus contribute to the cytotoxic effects of the drug.

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. 45, Issue 5
1 May 1994
  • 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.
Template 2-chloro-2'-deoxyadenosine monophosphate inhibits in vitro DNA synthesis.
(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

Template 2-chloro-2'-deoxyadenosine monophosphate inhibits in vitro DNA synthesis.

P Hentosh and P Grippo
Molecular Pharmacology May 1, 1994, 45 (5) 955-961;

Citation Manager Formats

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

Share
Abstract

Template 2-chloro-2'-deoxyadenosine monophosphate inhibits in vitro DNA synthesis.

P Hentosh and P Grippo
Molecular Pharmacology May 1, 1994, 45 (5) 955-961;
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 © 2023 by the American Society for Pharmacology and Experimental Therapeutics