Application of Liposome Based Sensors in High-Throughput Screening Systems

Abstract

High throughout screening is an approach based on the concept which assumes that when sufficiently large library of compounds are tested, the chance of discovering a new active compound is increased. In order to meet this expectation, proper testing criteria need to be devised. Those criteria should be related to the fate of a compound in the organism to have any predictive power. Not long ago, the main criteria were based exclusively on parameters defined by the maximum activity (QSAR). In this system the activity criteria have not been included therefore the compound ability to reach the target is not accounted for. Considering that, the construction of yet another set of parameters has been initiated (QSPR). The parameters are in fact semi-empirical numbers which need to be tested on real, physical models. Whereas the activity tests are straightforward, the pharmacokinetic ones are difficult and controversial. One such parameter describes the critical property of an active compound, namely its ability to cross biological membranes. This review describes new concepts in the determination of the permeability coefficient with the help of methods which are based on liposome biosensors. Two methods using fluorescence probes incorporated in the lipid bilayer of liposome are described in detail and compared to other currently available techniques.

Application of polymersomes in membrane protein study and drug discovery: Progress, strategies, and perspectives

“… 192 MP inserted nano‐vesicles such as proteopolymersomes and proteoliposomes, either freely residing in microplates or immobilized onto a membrane bilayer, serve as excellent cell‐free HTS platforms (Figure 8a ). 196 , 197 …”

“…192 MP inserted nano-vesicles such as proteopolymersomes and proteoliposomes, either freely residing in microplates or immobilized onto a membrane bilayer, serve as excellent cell-free HTS platforms (Figure 8a). 196,197 7.1 | Structural and conformational screening HTS of small molecules can be performed based on either modulating the protein-protein interactions (PPIs) 198,199 or perturbation of protein conformational dynamics, which directly corresponds to protein functions. 200,201 For example, multiple receptors form preligand dimers or undergo conformational changes upon ligand binding to exert their functions.…”

Liposomes in biosensors

“…Liposomes containing probe molecules have been utilized as cell membrane models in the screening of drugs, 214,215 investigation of the interaction between protein and cell membrane, simulation apoptosis of cells, 216 among other functions. Noda et al investigated the interactions between protein and cell membranes through leakage of the electrochemical marker as K 4 [Fe(CN) 6 ] from liposomes.…”