By the same authors

From the same journal

Targeting protein-protein interactions and fragment-based drug discovery

Research output: Contribution to journalReview article

Published copy (DOI)

Author(s)

Department/unit(s)

Publication details

JournalTopics in Current Chemistry
DatePublished - 2012
Volume317
Number of pages35
Pages (from-to)145-79
Original languageEnglish

Abstract

Protein-protein interactions (PPI) are integral to the majority of biological functions. Targeting these interactions with small molecule inhibitors is of increased interest both in academia as well as in the pharmaceutical industry, both for therapeutic purposes and in the search for chemical tools for basic science. Although the number of well-characterised examples is still relatively modest, it is becoming apparent that many different kinds of interactions can be inhibited using drug-like small molecules. Compared to active site targeting, PPI inhibition suffers from the particular problem of more exposed and less defined binding sites, and this imposes significant experimental challenges to the development of PPI inhibitors. PPI interfaces are large, up to thousands of square angstroms, and there is still debate as to what part of the interface one should target. We will review recent developments in the field of PPI inhibition, with emphasis on fragment-based methods, and discuss various factors one should take into account when developing small molecule inhibitors targeted at PPI interfaces.

    Research areas

  • Binding Sites/drug effects, Drug Discovery, Molecular Targeted Therapy, Protein Binding/drug effects, Protein Interaction Maps/drug effects, Proteins/antagonists & inhibitors, Small Molecule Libraries/chemistry, Structure-Activity Relationship

Discover related content

Find related publications, people, projects, datasets and more using interactive charts.

View graph of relations