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Two‐Step Synthesis of a Clickable Photoaffinity Probe from an Anticancer Saponin OSW‐1 and its Photochemical Reactivity
Author(s) -
Yamada Rika,
Hiraizumi Masato,
Narita Sho,
Sakurai Kaori
Publication year - 2016
Publication title -
asian journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.846
H-Index - 44
eISSN - 2193-5815
pISSN - 2193-5807
DOI - 10.1002/ajoc.201500505
Subject(s) - chemistry , photoaffinity labeling , linker , click chemistry , stereochemistry , reactivity (psychology) , acylation , saponin , combinatorial chemistry , binding site , biochemistry , medicine , catalysis , alternative medicine , pathology , computer science , operating system
OSW‐1 is a highly potent anticancer saponin with an unknown mechanism of action that is distinct from the currently used chemotherapeutic agents. Toward investigation of its binding proteins, we designed and synthesized a clickable photoaffinity probe from OSW‐1 and characterized its photochemical reactivity. A mild, two‐step procedure involving a Me 2 SnCl 2 ‐mediated acylation reaction was developed to site‐selectively derivatize OSW‐1 with a linker that bears a photoreactive group and an alkyne tag. The OSW‐1‐based photoaffinity probe retained potent anticancer activity similar to that of the parent natural product, thereby providing a cell‐permeable analogue of OSW‐1. Photoaffinity labeling studies demonstrated that the probe enabled crosslinking of a model sterol‐binding protein in an affinity‐dependent fashion, which could be efficiently detected by conjugating a fluorophore or biotin by click chemistry.