Issue 4, 2019

Microflow-based dynamic combinatorial chemistry: a microscale synthesis and screening platform for the rapid and accurate identification of bioactive molecules

Abstract

Protein-directed dynamic combinatorial chemistry (DCC) has emerged as an efficient tool for the rapid identification of bioactive molecules in modern drug discovery. However, the applications of protein-directed DCC have been significantly hampered by (i) the poor reactivity of potential inhibitors at low concentration; (ii) the reduction of protein activity or the decomposition of potential inhibitors owing to long equilibration times; and (iii) limited analytical detection methods capable of processing large libraries. Here we report the development of a rapid flow-based synthesis and screening platform that integrates both microscale synthesis and identification of protein binders from protein-directed dynamic libraries into a single modular unit. By using microflow synthesis, the processes of compound synthesis and binding to the target protein were accelerated, and the accuracy of identification of potential inhibitors was improved. This system was validated by a case study that identified competitive inhibitors of bovine serum albumin (BSA). A significant reduction in equilibration time and an increased sensitivity for the identification of protein binders were acquired. Owing to the microscale effect, a new inhibitor for BSA, which was not found in batch mode, was discovered in the microflow system and the interaction of the new binder with BSA was also investigated.

Graphical abstract: Microflow-based dynamic combinatorial chemistry: a microscale synthesis and screening platform for the rapid and accurate identification of bioactive molecules

Supplementary files

Article information

Article type
Communication
Submitted
07 Des 2018
Accepted
22 Feb 2019
First published
23 Feb 2019

React. Chem. Eng., 2019,4, 658-662

Microflow-based dynamic combinatorial chemistry: a microscale synthesis and screening platform for the rapid and accurate identification of bioactive molecules

C. Qiu, Z. Fang, L. Zhao, W. He, Z. Yang, C. Liu and K. Guo, React. Chem. Eng., 2019, 4, 658 DOI: 10.1039/C8RE00327K

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements