HUDSPITH, Lewis, SHMAM, Faraj, DALTON, Caroline F, PRINCIVALLE, Alessandra and TUREGA, Simon (2019). Neurotransmitter selection by monoamine oxidase isoforms, dissected in terms of functional groups by mixed double mutant cycles. Organic & Biomolecular Chemistry.
|
PDF
Turega-NeurotransmitterMonoamineOxidase(AM).pdf - Accepted Version All rights reserved. Download (866kB) | Preview |
Abstract
Double mutant cycles were constructed using neurotransmitters and synthetic substrates that measure their selective binding to one monoamine oxidase (MAO) enzyme isoform over another as a function of structural change. This work measures a reduction in selectivity for the MAOB isoform of 3 to 9.5 kJ mol−1 upon the addition of hydroxy functional groups to a phenethylamine scaffold. Replacement of hydroxy functional groups on the phenethylamine scaffold by hydrophobic substituents measures an increase in selectivity for MAOB of −1.1 to −6.9 kJ mol−1. The strategies presented here can be applied to the development of competitive reversible inhibitors of MAO enzymes and other targets with structurally related isoforms.
Item Type: | Article |
---|---|
Uncontrolled Keywords: | Organic Chemistry; 0304 Medicinal and Biomolecular Chemistry; 0305 Organic Chemistry; 1115 Pharmacology and Pharmaceutical Sciences |
Identification Number: | https://doi.org/10.1039/c9ob01558b |
SWORD Depositor: | Symplectic Elements |
Depositing User: | Symplectic Elements |
Date Deposited: | 30 Sep 2019 11:57 |
Last Modified: | 17 Mar 2021 22:46 |
URI: | https://shura.shu.ac.uk/id/eprint/25186 |
Actions (login required)
View Item |
Downloads
Downloads per month over past year