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A two-step resin based approach to reveal survivin-selective fluorescent probes.

ABSTRACT: The identification of modulators for proteins without assayable biochemical activity remains a challenge in chemical biology. The presented approach adapts a high-throughput fluorescence binding assay and functional chromatography, two protein-resin technologies, enabling the discovery and isolation of fluorescent natural product probes that target proteins independently of biochemical function. The resulting probes also suggest targetable pockets for lead discovery. Using human survivin as a model, we demonstrate this method with the discovery of members of the prodiginine family as fluorescent probes to the cancer target survivin.

SUBMITTER: Ambrose AJ

PROVIDER: S-EPMC8342005 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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A two-step resin based approach to reveal survivin-selective fluorescent probes.

Ambrose Andrew J AJ Pham Nhan T NT Sivinski Jared J Guimarães Larissa L Mollasalehi Niloufar N Jimenez Paula P Abad Maria A MA Jeyaprakash A Arockia AA Shave Steven S Costa-Lotufo Letícia V LV La Clair James J JJ Auer Manfred M Chapman Eli E

RSC chemical biology 20201127 1

The identification of modulators for proteins without assayable biochemical activity remains a challenge in chemical biology. The presented approach adapts a high-throughput fluorescence binding assay and functional chromatography, two protein-resin technologies, enabling the discovery and isolation of fluorescent natural product probes that target proteins independently of biochemical function. The resulting probes also suggest targetable pockets for lead discovery. Using human survivin as a mo ...[more]

PMID: 34458780

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