Related Experiment Video
Updated: Feb 12, 2026

From Molecules to Materials: Engineering New Ionic Liquid Crystals Through Halogen Bonding
Published on: March 24, 2018
Halogen-Aromatic π Interactions Modulate Inhibitor Residence Times
Christina Heroven1, Victoria Georgi2, Gaurav K Ganotra3,4
1Nuffield Department of Clinical Medicine, Structural Genomics Consortium, University of Oxford, Oxford, OX3 7DQ, UK.
Abstract:
Prolonged drug residence times may result in longer-lasting drug efficacy, improved pharmacodynamic properties, and "kinetic selectivity" over off-targets with high drug dissociation rates. However, few strategies have been elaborated to rationally modulate drug residence time and thereby to integrate this key property into the drug development process. Herein, we show that the interaction between a halogen moiety on an inhibitor and an aromatic residue in the target protein can significantly increase inhibitor residence time. By using the interaction of the serine/threonine kinase haspin with 5-iodotubercidin (5-iTU) derivatives as a model for an archetypal active-state (type I) kinase-inhibitor binding mode, we demonstrate that inhibitor residence times markedly increase with the size and polarizability of the halogen atom. The halogen-aromatic π interactions in the haspin-inhibitor complexes were characterized by means of kinetic, thermodynamic, and structural measurements along with binding-energy calculations.
More Related Videos
10:33Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors
Published on: October 26, 2015
10:53Anionic Polymerization of an Amphiphilic Copolymer for Preparation of Block Copolymer Micelles Stabilized by π-π Stacking Interactions
Published on: October 10, 2016
Related Concept Videos
Noncompartmental Analysis: Mean Residence Time
After the administration of a drug through intravenous bolus injection, the drug molecules are distributed throughout the body and remain there for varying periods. The MRT represents the average time these drug molecules stay in the...
Halogens
π Electron Effects on Chemical Shift: Aromatic and Antiaromatic Compounds
Eukaryotic Transcription Inhibitors
Eukaryotic transcription inhibitors usually contain two distinct domains, a...
Nucleophilic Aromatic Substitution of Aryldiazonium Salts: Aromatic SN1
In the Sandmeyer reaction, for example, the diazonio group is replaced by a chloro, bromo,...
π Molecular Orbitals of 1,3-Butadiene
The simplest conjugated diene is 1,3-butadiene: a four-carbon system where each carbon is sp2-hybridized and has an unhybridized p orbital that contains an unpaired electron. According to molecular orbital theory, atomic orbitals combine to form molecular orbitals such that the number...