Methods and techniques of capillary electrophoresis for drug screening

doi:10.3724/SP.J.1123.2020.05040

Abstract

Abstract:

Capillary electrophoresis (CE) shows enormous potential for application in new drug research and development. Because of the aqueous medium employed as the running buffer in CE, drug screening can be carried out in an environment similar to that in physiological testing media. Drug screening methods based on CE are different from other instrumental measurements in vitro. CE can not only sustain the biological activity of the screened molecules and ligands, but also help evaluate the interactions between the receptors and the ligands. Based on these interactions, some important pharmacological parameters related to drug screening, such as the association constant K_b , bonding rate constant K_on , and dissociation rate constant K_off , can be determined by CE. Thus, CE is an effective tool for simulating and predicting the entire interaction process between receptors and drugs in vivo. In this review, the history of CE for drug screening is revisited. The theories, common methods for drug screening by CE, and some application examples and related technologies are reviewed. The methods of drug screening by means of affinity CE and kinetic CE are introduced. Some selected studies on different ligands at the molecular and cellular level are reported, along with examples several types of drugs. Techniques based on a combination of CE with mass spectrometry and chemiluminescence are reviewed, with focus on the screening of candidate drugs and active compounds from traditional Chinese medicine. The application prospect of drug screening by CE combined with a DNA-encoded compound library is introduced. This paper discusses the core of the fraction collection step in CE and emphasizes the significance of combining CE with systematic evolution of ligands by exponential enrichment. In conclusion, various optional methods for CE drug screening would pave the way for new concepts related to drug screening and evaluation in the future.

Key words: capillary electrophoresis (CE), drug screening, interaction, DNA encoded compound library, activity evaluation, review

QIAN Xin, TIAN Yan, LUO Xinxin, PAN Jingmiao, DENG Suya, HUANG Yike, FU Qifeng, XIA Zhining. Methods and techniques of capillary electrophoresis for drug screening[J]. Chinese Journal of Chromatography, 2020, 38(10): 1170-1178.

Figures/Tables 2

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Method	Diagram
NECEEM: nonequilibrium capillary electrophoresis of equilibrium mixture; ECEEM: equilibrium capillary electrophoresis of equilibrium mixture; Sweep CE: sweep capillary electrophoresis; ppKCE: plug-plug kinetic capillary electrophoresis; cNECEEM: continuous nonequilibrium capillary electrophoresis of equilibrium mixture; sSweep CE: short sweep capillary electrophoresis; sSweep CEEM: short sweep capillary electrophoresis of equilibrium mixtures; T: target; L: ligand; EM: equilibrium mixture.
NECEEM
ECEEM
Sweep CE
ppKCE
cNECEEM
sSweep CE
sSweep CEEM

Method	Diagram
NECEEM: nonequilibrium capillary electrophoresis of equilibrium mixture; ECEEM: equilibrium capillary electrophoresis of equilibrium mixture; Sweep CE: sweep capillary electrophoresis; ppKCE: plug-plug kinetic capillary electrophoresis; cNECEEM: continuous nonequilibrium capillary electrophoresis of equilibrium mixture; sSweep CE: short sweep capillary electrophoresis; sSweep CEEM: short sweep capillary electrophoresis of equilibrium mixtures; T: target; L: ligand; EM: equilibrium mixture.
NECEEM
ECEEM
Sweep CE
ppKCE
cNECEEM
sSweep CE
sSweep CEEM

Mechanism	Method	Sample	Running solution	Diagram	Condition	Parameter	Ref.
ACE: affinity capillary electrophoresis; VACE: vacancy affinity capillary electrophoresis; LS: ligand separation; VP: vacancy peak; HD: Hummel-Dreyer; FA: frontier analysis; D: drug; P: protein; μ_D : drug mobility; μ_P : protein mobility; μ_DP : complex mobility; t_m : migration time; A : peak area; H : peak height.
According to mobility change	ACE	D/P	P/D+buffer		μ_DP ≠μ_D	t_m	[14, 15]
	VACE	buffer	D+P+buffer		μ_DP ≠μ_D	t_m	[29]
According to concentration	LS	D+P	buffer		μ_DP =μ_P	A	[26, 27]
change	VP	buffer	D+P+buffer		μ_DP =μ_P	A	[8]
	HD	D+P+buffer	D+buffer		μ_DP =μ_P	A	[30]
	FA	D+P+buffer	buffer		μ_DP =μ_P & μ_D ≠μ_P	H	[31]

Mechanism	Method	Sample	Running solution	Diagram	Condition	Parameter	Ref.
ACE: affinity capillary electrophoresis; VACE: vacancy affinity capillary electrophoresis; LS: ligand separation; VP: vacancy peak; HD: Hummel-Dreyer; FA: frontier analysis; D: drug; P: protein; μ_D : drug mobility; μ_P : protein mobility; μ_DP : complex mobility; t_m : migration time; A : peak area; H : peak height.
According to mobility change	ACE	D/P	P/D+buffer		μ_DP ≠μ_D	t_m	[14, 15]
	VACE	buffer	D+P+buffer		μ_DP ≠μ_D	t_m	[29]
According to concentration	LS	D+P	buffer		μ_DP =μ_P	A	[26, 27]
change	VP	buffer	D+P+buffer		μ_DP =μ_P	A	[8]
	HD	D+P+buffer	D+buffer		μ_DP =μ_P	A	[30]
	FA	D+P+buffer	buffer		μ_DP =μ_P & μ_D ≠μ_P	H	[31]

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