Partitioning of Catechol Derivatives in Lipid Membranes : Implications for Substrate Specificity to Catechol-O-methyltransferase

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Parkkila , P & Viitala , T 2020 , ' Partitioning of Catechol Derivatives in Lipid Membranes : Implications for Substrate Specificity to Catechol-O-methyltransferase ' , ACS chemical neuroscience , vol. 11 , no. 6 , pp. 969-978 . https://doi.org/10.1021/acschemneuro.0c00049

Title: Partitioning of Catechol Derivatives in Lipid Membranes : Implications for Substrate Specificity to Catechol-O-methyltransferase
Author: Parkkila, Petteri; Viitala, Tapani
Contributor organization: Pharmaceutical biophysics group
Division of Pharmaceutical Biosciences
Drug Research Program
Division of Pharmaceutical Chemistry and Technology
Date: 2020-03-18
Language: eng
Number of pages: 10
Belongs to series: ACS chemical neuroscience
ISSN: 1948-7193
DOI: https://doi.org/10.1021/acschemneuro.0c00049
URI: http://hdl.handle.net/10138/314639
Abstract: We have utilized multiparametric surface plasmon resonance and impendance-based quartz crystal microbalance instruments to study the distribution coefficients of catechol derivatives in cell model membranes. Our findings verify that the octanol-water partitioning coefficient is a poor descriptor of the total lipid affinity for small molecules which show limited lipophilicity in the octanol-water system. Notably, 3-methoxytyramine, the methylated derivative of the neurotransmitter dopamine, showed substantial affinity to the lipids despite its nonlipophilic nature predicted by octanol-water partitioning. The average ratio of distribution coefficients between 3-methoxytyramine and dopamine was 8.0. We also found that the interactions between the catechols and the membranes modeling the cell membrane outer leaflet are very weak, suggesting a mechanism other than the membrane-mediated mechanism of action for the neurotransmitters at the postsynaptic site. The average distribution coefficient for these membranes was one-third of the average value for pure phosphatidylcholine membranes, calculated using all compounds. In the context of our previous work, we further theorize that membrane-bound enzymes can utilize membrane headgroup partitioning to find their substrates. This could explain the differences in enzyme affinity between soluble and membrane-bound isoforms of catechol-O-methyltransferase, an essential enzyme in catechol metabolism.
Subject: Catechols
partition coefficient
distribution coefficient
supported lipid bilayer
multiparametric surface plasmon resonance
quartz crystal microbalance
SURFACE-PLASMON RESONANCE
DRUG DISCOVERY
IN-VITRO
DOPAMINE
MODEL
PERMEABILITY
ANESTHETICS
ENTACAPONE
MECHANISM
TOLCAPONE
1182 Biochemistry, cell and molecular biology
317 Pharmacy
3112 Neurosciences
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion


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