Department of Biotechnology, Translational Research Center for Protein Function Control, College of Life Science & Biotechnology, Yonsei University, Seoul 120-749, Republic of Korea.
Nat Prod Rep. 2016 May 4;33(5):719-30. doi: 10.1039/c5np00107b.
Covering: up to February 2016Identification of the target proteins of natural products is pivotal to understanding the mechanisms of action to develop natural products for use as molecular probes and potential therapeutic drugs. Affinity chromatography of immobilized natural products has been conventionally used to identify target proteins, and has yielded good results. However, this method has limitations, in that labeling or tagging for immobilization and affinity purification often result in reduced or altered activity of the natural product. New strategies have recently been developed and applied to identify the target proteins of natural products and synthetic small molecules without chemical modification of the natural product. These direct and indirect methods for target identification of label-free natural products include drug affinity responsive target stability (DARTS), stability of proteins from rates of oxidation (SPROX), cellular thermal shift assay (CETSA), thermal proteome profiling (TPP), and bioinformatics-based analysis of connectivity. This review focuses on and reports case studies of the latest advances in target protein identification methods for label-free natural products. The integration of newly developed technologies will provide new insights and highlight the value of natural products for use as biological probes and new drug candidates.
截至 2016 年 2 月
鉴定天然产物的靶蛋白对于了解作用机制至关重要，这有助于开发天然产物作为分子探针和有潜力的治疗药物。固定化天然产物的亲和层析已被常规用于鉴定靶蛋白，并取得了良好的效果。然而，该方法存在局限性，因为固定化和亲和纯化的标记或标记通常会导致天然产物的活性降低或改变。最近已经开发并应用了新的策略来鉴定天然产物和合成小分子的靶蛋白，而无需对天然产物进行化学修饰。这些用于鉴定无标记天然产物靶标的直接和间接方法包括药物亲和反应靶标稳定性（DARTS）、氧化速率的蛋白质稳定性（SPROX）、细胞热转移测定（CETSA）、热蛋白质组学分析（TPP）和基于生物信息学的连接性分析。本综述重点介绍并报告了无标记天然产物靶蛋白鉴定方法的最新进展的案例研究。新技术的整合将提供新的见解，并强调天然产物作为生物探针和新药候选物的价值。
