Intestinal transport of TRH analogs through PepT1: the role of in silico and in vitro modeling

The present study involves molecular docking, molecular dynamics (MD) simulation studies, and Caco‐2 cell monolayer permeability assay to investigate the effect of structural modifications on PepT1‐mediated transport of thyrotropin releasing hormone (TRH) analogs. Molecular docking of four TRH analo...

Full description

Saved in:
Bibliographic Details
Published in:Journal of molecular recognition 2014-10, Vol.27 (10), p.609-617
Main Authors: Bagul, Pravin, Khomane, Kailas S., Kesharwani, Siddharth S., Pragyan, Preeti, Nandekar, Prajwal P., Meena, Chhuttan Lal, Bansal, Arvind K., Jain, Rahul, Tikoo, Kulbhushan, Sangamwar, Abhay T.
Format: Article
Language:English
Subjects:
Analogs
Binding
Binding Sites
Biological Transport
Caco-2 Cells
Chromatography, High Pressure Liquid
Computational Biology
Computer Simulation
Docking
Drugs
GastroPlus
Humans
In vitro testing
Intestines - metabolism
Models, Molecular
molecular docking
Molecular dynamics
Molecular Dynamics Simulation
PepT1-mediated transport
Peptide Transporter 1
Permeability
Symporters - chemistry
Symporters - metabolism
Symporters - physiology
Thyrotropin-Releasing Hormone - analogs & derivatives
Thyrotropin-Releasing Hormone - chemistry
Thyrotropin-Releasing Hormone - pharmacokinetics
Transport
TRH analogs
Citations: Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The present study involves molecular docking, molecular dynamics (MD) simulation studies, and Caco‐2 cell monolayer permeability assay to investigate the effect of structural modifications on PepT1‐mediated transport of thyrotropin releasing hormone (TRH) analogs. Molecular docking of four TRH analogs was performed using a homology model of human PepT1 followed by subsequent MD simulation studies. Caco‐2 cell monolayer permeability studies of four TRH analogs were performed at apical to basolateral and basolateral to apical directions. Inhibition experiments were carried out using Gly‐Sar, a typical PepT1 substrate, to confirm the PepT1‐mediated transport mechanism of TRH analogs. Papp of the four analogs follows the order: NP‐1894 
ISSN:0952-3499
1099-1352
DOI:10.1002/jmr.2385