Site-directed Late-stage Diversification of Macrocyclic Nannocystins Facilitating Anticancer SAR and Mode of Action Studies

Overview

Journal RSC Med Chem

Publisher Royal Society of Chemistry

Specialty Chemistry

Date 2023 Feb 27

PMID 36846368

Authors

Han Zhang

Yunfeng Tian

Xiaoya Yuan

Fei Xie

Siqi Yu

Jiayou Cai

Bin Sun

Changliang Shan

Weicheng Zhang

Affiliations

Soon will be listed here.

Abstract

Nannocystins are a family of 21-membered cyclodepsipeptides with excellent anticancer activity. However, their macrocyclic architecture poses a significant challenge to structure modification. Herein, this issue is addressed by leveraging the strategy of post-macrocyclization diversification. In particular, a novel serine-incorporating nannocystin was designed so that its appending hydroxyl group could diversify into a wide variety of side chain analogues. Such effort facilitated not only structure-activity correlation at the subdomain of interest, but also the development of a macrocyclic coumarin-labeled fluorescence probe. Uptake experiments indicated good cell permeability of the probe, and endoplasmic reticulum was identified as its subcellular localization site.

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