3-D-QSAR and docking studies on the neuronal choline transporter

Bioorganic & Medicinal Chemistry Letters
Werner J GeldenhuysPaul R Lockman

Abstract

The high affinity neuronal choline transporter (CHT1) is responsible for the uptake of choline into the pre-synaptic terminal of cholinergic neurons. Considering our past experience with modeling the blood-brain barrier choline transporter (BBBCHT) as drug delivery vector to the CNS, we investigated the 3-D-quantitative structure-activity relationship of the neuronal choline transporter. Comparative molecular field analysis (CoMFA) and comparative similarity index analysis (CoMSIA) yielded cross-validated models with a q(2) of 0.5, and a non-cross validated r(2) of 0.8. The electrostatic results of the 3-D-QSAR models are corroborated with a docking study into the bacterial choline transporter. Using this electrostatic map, we propose a putative binding site in a homology model of the CHT1. Knowledge gained from this study is useful to better understand the CHT1 as well as can be used in medicinal chemistry programs targeting this transporter.

References

Jan 26, 1973·Biochimica Et Biophysica Acta·T Haga, H Noda
Nov 10, 1972·Science·H I Yamamura, S H Snyder
May 17, 2005·Drug Discovery Today·Cheng ChangPeter Swaan

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Citations

Feb 1, 2011·Environmental Microbiology Reports
Mar 13, 2021·Bioorganic & Medicinal Chemistry Letters·Werner J Geldenhuys, Jeffrey R Bloomquist

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