A simple and sensitive detection of small molecule–protein interactions based on terminal protection-mediated exponential strand displacement amplification

The Analyst ◽  
2018 ◽  
Vol 143 (9) ◽  
pp. 2023-2028 ◽  
Author(s):  
Chang Yeol Lee ◽  
Hyo Yong Kim ◽  
Soeun Kim ◽  
Ki Soo Park ◽  
Hyun Gyu Park
Keyword(s):  
Small Molecule ◽  
Protein Interaction ◽  
Protein Interactions ◽  
Sensitive Detection ◽  
Strand Displacement ◽  
Strand Displacement Amplification ◽  
New Strategy

A new strategy to detect a small molecule–protein interaction was devised based on terminal protection-mediated exponential strand displacement amplification (eSDA).

scholarly journals Development of a Split Esterase for Protein-Protein Interaction Dependent Small Molecule Activation

2019 ◽  
Author(s):  
Krysten A. Jones ◽  
Kaitlin Kentala ◽  
Michael Beck ◽  
Weiwei An ◽  
Alexander Lippert ◽  
...  
Keyword(s):  
Synthetic Biology ◽  
Small Molecule ◽  
Protein Interaction ◽  
Protein Interactions ◽  
Cell Killing ◽  
Dependent Manner ◽  
Protein Protein Interactions ◽  
Protein Protein Interaction ◽  
Cytotoxic Molecule ◽  
Measured Input

Split reporters based on fluorescent proteins and luciferases have emerged as valuable tools for measuring interactions in biological systems. Relatedly, biosensors that transduce measured input signals into outputs that influence the host system are key components of engineered gene circuits for synthetic biology applications. While small molecule-based imaging agents are widely used in biological studies, and small molecule-based drugs and chemical probes can target a range of biological processes, a general method for generating a target small molecule in a biological system based on a measured input signal is lacking. Here, we develop a proximity-dependent split esterase that selectively unmasks ester-protected small molecules in an interaction-dependent manner. Exploiting the versatility of an ester-protected small molecule output, we demonstrate fluorescent, chemiluminescent, and pharmacological probe generation, each created by masking key alcohol functional groups on a target small molecule. We show the split esterase system can be used in combination with ester-masked fluorescent or luminescent probes to measure a protein-protein interactions and protein-protein interaction inhibitor engagement. We demonstrate the esterase-based reporter system is compatible with other commonly-used split reporter imaging systems for the simultaneous detection of multiple protein-protein interactions. Finally, we develop a system for selective small molecule-dependent cell killing by unmasking a cytotoxic molecule using an inducible split esterase. Presaging utility in future synthetic biology-based therapeutic applications, we also show the system can be used for intercellular cell killing via a bystander effect, where one activated cell unmasks a cytotoxic molecule and kills cells physically adjacent to the activated cells. Collectively, this work illustrates that the split esterase system is a valuable new addition to the split protein toolbox, with particularly exciting potential in synthetic biology applications.

Simultaneously sensitive detection of multiple miRNAs based on a strand displacement amplification

2013 ◽  
Vol 49 (1) ◽  
pp. 75-77 ◽  
Author(s):  
Tian Tian ◽  
Heng Xiao ◽  
Xiaolian Zhang ◽  
Shuang Peng ◽  
Xiaoe Zhang ◽  
...  
Keyword(s):  
Sensitive Detection ◽  
Strand Displacement ◽  
Strand Displacement Amplification

A systematic molecular dynamics approach to the study of peptide Keap1–Nrf2 protein–protein interaction inhibitors and its application to p62 peptides

2016 ◽  
Vol 12 (4) ◽  
pp. 1378-1387 ◽  
Author(s):  
Meng-Chen Lu ◽  
Zhen-Wei Yuan ◽  
Yong-Lin Jiang ◽  
Zhi-Yun Chen ◽  
Qi-Dong You ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Small Molecule ◽  
Protein Interaction ◽  
Protein Interactions ◽  
Drug Targets ◽  
Protein Protein Interactions ◽  
Protein Protein Interaction ◽  
P Protein ◽  
Nrf2 Protein

Protein–protein interactions (PPIs) as drug targets have been gaining growing interest, though developing drug-like small molecule PPI inhibitors remains challenging.

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