Target discovery of bioactive natural products with native-compound-coupled CNBr-activated Sepharose 4B beads (NCCB): Applications, mechanisms and outlooks

Yueteng Zhang, Junjie Zhang, Menglong Li, Yan Qiao, Wei Wang, Lu Ma, Kangdong Liu

Research output: Contribution to journalReview articlepeer-review

Abstract

Natural products (NPs) represent a treasure trove for drug discovery and development due to their chemical structural diversity and a broad spectrum of biological activities. Uncovering the biological targets and understanding their molecular mechanism of actions are crucial steps in the development of clinical therapeutics. However, the structural complexity of NPs and intricate nature of biological system present formidable challenges in target identification of NPs. Although significant advances have been made in the development of new chemical tools, these methods often require high levels of synthetic skills for preparing chemical probes. This can be costly and time-consuming relaying on operationally complicated procedures and instruments. In recent efforts, we and others have successfully developed an operationally simple and practical chemical tool known as native-compound-coupled CNBr-activated Sepharose 4B beads (NCCB) for NP target identification. In this approach, a native compound readily reacts with commercial CNBr-activated Sepharose 4B beads with a process that is easily performed in any biology laboratory. Based on NCCB, our group has identified the direct targets of more than 60 NPs. In this review, we will elucidate the application scopes, including flavonoids, quinones, terpenoids and others, characteristics, chemical mechanisms, procedures, advantages, disadvantages, and future directions of NCCB in specific target discovery.

Original languageEnglish (US)
Article number117483
JournalBioorganic and Medicinal Chemistry
Volume96
DOIs
StatePublished - Dec 15 2023

Keywords

  • CNBr-activated Sepharose 4B beads
  • Chemical proteomics
  • Mechanism of action
  • Natural products
  • Target discovery

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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