Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • 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
  • 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
    • 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
  • Visit molpharm on Facebook
  • Follow molpharm on Twitter
  • Follow molpharm on LinkedIn
Research ArticleArticle

Ligand Specificity of the Genetic Variants of Human α1-Acid Glycoprotein: Generation of a Three-Dimensional Quantitative Structure-Activity Relationship Model for Drug Binding to the A Variant

Françoise Hervé, Giulia Caron, Jean-Claude Duché, Patrick Gaillard, Noorsaadah Abd. Rahman, Anna Tsantili-Kakoulidou, Pierre-Alain Carrupt, Philippe d’Athis, Jean-Paul Tillement and Bernard Testa
Molecular Pharmacology July 1998, 54 (1) 129-138; DOI: https://doi.org/10.1124/mol.54.1.129
Françoise Hervé
1 2 3
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Giulia Caron
1 2 3
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jean-Claude Duché
1 2 3
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Patrick Gaillard
1 2 3
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Noorsaadah Abd. Rahman
1 2 3
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Anna Tsantili-Kakoulidou
1 2 3
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Pierre-Alain Carrupt
1 2 3
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Philippe d’Athis
1 2 3
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jean-Paul Tillement
1 2 3
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Bernard Testa
1 2 3
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF
Loading

Abstract

Human α1-acid glycoprotein (AAG) is a mixture of at least two genetic variants: the A variant and the F1 and/or S variant or variants, which are encoded by two different genes. In a continuation of previous studies indicating specific drug transport roles for each AAG variant according to its separate genetic origin, this work was designed to (1) determine the affinities of the two main gene products of AAG (i.e., the A variant and a mixture of the F1 and S variants) for 35 chemically diverse drugs and (2) to obtain meaningful 3D-QSARs for each binding site. Affinities were obtained by displacement experiments, leading to qualitative indications about binding site characteristics. In particular, drugs binding selectively to the A variant displayed some common structural features, but this was not seen for the F1*S variants. Three-dimensional QSAR analyses using the CoMFA method yielded a steric model for binding to the A variant, from which a simplified haptophoric model was derived. In contrast, no statistically sound model was found for the F1*S variants, possibly due (among other reasons) to an insufficient number of high affinity ligands in the set.

Footnotes

    • Received August 1, 1997.
    • Accepted March 16, 1998.
  • Send reprint requests to: Prof. Bernard Testa, School of Pharmacy, BEP, University of Lausanne, CH-1015 Lausanne, Switzerland. E-mail: bernard.testa{at}ict.unil.ch

  • ↵1 Current affiliation: Department of Chemistry, University of Malaya, 50603 Kuala Lumpur, Malaysia.

  • B.T. and P.A.C. are indebted to the Swiss National Science Foundation for support. F.H., J.C.D., and J.P.T. are indebted to the Ministère de l’Education Nationale (EA 427) and to the Réseau de Pharmacologie Clinique for support. N.A.R. acknowledges receipt of a JWT Jones Travelling Fellowship given by the Royal Society of Chemistry. A.T.K. is indebted to the Foundation Herbette (University of Lausanne) for a travel grant. F.H. and G.C. contributed equally to this study.

  • The American Society for Pharmacology and Experimental Therapeutics
View Full Text

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: 54 (1)
Molecular Pharmacology
Vol. 54, Issue 1
1 Jul 1998
  • Table of Contents
  • About the Cover
  • Index by author
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.
Ligand Specificity of the Genetic Variants of Human α1-Acid Glycoprotein: Generation of a Three-Dimensional Quantitative Structure-Activity Relationship Model for Drug Binding to the A Variant
(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
Research ArticleArticle

Ligand Specificity of the Genetic Variants of Human α1-Acid Glycoprotein: Generation of a Three-Dimensional Quantitative Structure-Activity Relationship Model for Drug Binding to the A Variant

Françoise Hervé, Giulia Caron, Jean-Claude Duché, Patrick Gaillard, Noorsaadah Abd. Rahman, Anna Tsantili-Kakoulidou, Pierre-Alain Carrupt, Philippe d’Athis, Jean-Paul Tillement and Bernard Testa
Molecular Pharmacology July 1, 1998, 54 (1) 129-138; DOI: https://doi.org/10.1124/mol.54.1.129

Citation Manager Formats

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

Ligand Specificity of the Genetic Variants of Human α1-Acid Glycoprotein: Generation of a Three-Dimensional Quantitative Structure-Activity Relationship Model for Drug Binding to the A Variant

Françoise Hervé, Giulia Caron, Jean-Claude Duché, Patrick Gaillard, Noorsaadah Abd. Rahman, Anna Tsantili-Kakoulidou, Pierre-Alain Carrupt, Philippe d’Athis, Jean-Paul Tillement and Bernard Testa
Molecular Pharmacology July 1, 1998, 54 (1) 129-138; DOI: https://doi.org/10.1124/mol.54.1.129
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Experimental Procedures
    • Results
    • Discussion
    • Footnotes
    • Abbreviations
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Identification of Celecoxib targets by label-free TPP
  • Editing TOP2α Intron 19 5′ SS Circumvents Drug Resistance
  • CTS Bias
Show more Article

Similar Articles

  • 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 © 2021 by the American Society for Pharmacology and Experimental Therapeutics