alexa Predicting plasma protein binding of drugs: a new approach.
Bioinformatics & Systems Biology

Bioinformatics & Systems Biology

Journal of Proteomics & Bioinformatics

Author(s): Kratochwil NA, Huber W, Mller F, Kansy M, Gerber PR

Abstract Share this page

Abstract In spite of the large amount of plasma protein binding data for drugs, it is not obvious and there is no clear consensus among different disciplines how to deal with this parameter in multidimensional lead optimization strategies. In this work, we have made a comprehensive study on the importance of plasma protein binding and the influencing factors in order to get new insights for this molecular property. Our analysis of the distribution of percentage plasma protein binding among therapeutic drugs showed that no general rules for protein binding can be derived, except for the class of chemotherapeutics, where a clear trend towards lower binding could be observed. For the majority of indication areas, however, empirical rules are missing. We present here an extensive list of multiply determined primary association constants for binding to human serum albumin (HSA) for 138 compounds from the literature. Correlating these binding constants with the percentage fraction of protein bound showed that the percentage data above 90\%, corresponding to a binding constant below 6 microM, are of insufficient accuracy. Furthermore, it could be demonstrated that the lipophilicity of drugs, traditionally felt to dominate binding to HSA, is not the only relevant descriptor. Here, we report a generic model for the prediction of drug association constants to HSA, which uses a pharmacophoric similarity concept and partial least square analysis (PLS) to construct a quantitative structure-activity relationship. It is able to single out the submicromolar to nanomolar binders, i.e. to differentiate between 99.0 and 99.99\% plasma protein binding. Depending on the system, this can be important in medicinal chemistry programs and may together with other computed physicochemical and ADME properties assist in the prioritization of synthetic strategies.
This article was published in Biochem Pharmacol and referenced in Journal of Proteomics & Bioinformatics

Relevant Expert PPTs

Relevant Speaker PPTs

Recommended Conferences

  • 9th International Conference on Bioinformatics
    October 23-24, 2017 Paris, France
  • 9th International Conference and Expo on Proteomics
    October 23-25, 2017 Paris, France

Relevant Topics

Peer Reviewed Journals
 
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
 
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

Agri, Food, Aqua and Veterinary Science Journals

Dr. Krish

[email protected]

1-702-714-7001 Extn: 9040

Clinical and Biochemistry Journals

Datta A

[email protected]

1-702-714-7001Extn: 9037

Business & Management Journals

Ronald

[email protected]

1-702-714-7001Extn: 9042

Chemical Engineering and Chemistry Journals

Gabriel Shaw

[email protected]

1-702-714-7001 Extn: 9040

Earth & Environmental Sciences

Katie Wilson

[email protected]

1-702-714-7001Extn: 9042

Engineering Journals

James Franklin

[email protected]

1-702-714-7001Extn: 9042

General Science and Health care Journals

Andrea Jason

[email protected]

1-702-714-7001Extn: 9043

Genetics and Molecular Biology Journals

Anna Melissa

[email protected]

1-702-714-7001 Extn: 9006

Immunology & Microbiology Journals

David Gorantl

[email protected]

1-702-714-7001Extn: 9014

Informatics Journals

Stephanie Skinner

[email protected]

1-702-714-7001Extn: 9039

Material Sciences Journals

Rachle Green

[email protected]

1-702-714-7001Extn: 9039

Mathematics and Physics Journals

Jim Willison

[email protected]

1-702-714-7001 Extn: 9042

Medical Journals

Nimmi Anna

[email protected]

1-702-714-7001 Extn: 9038

Neuroscience & Psychology Journals

Nathan T

[email protected]

1-702-714-7001Extn: 9041

Pharmaceutical Sciences Journals

John Behannon

[email protected]

1-702-714-7001Extn: 9007

Social & Political Science Journals

Steve Harry

[email protected]

1-702-714-7001 Extn: 9042

 
© 2008-2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version
adwords