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Site-specific incorporation of quadricyclane into a protein and photocleavage of the quadricyclane ligation adduct.

ABSTRACT: The quadricyclane (QC) ligation is a bioorthogonal reaction between a quadricyclane moiety and a nickel bis(dithiolene) derivative. Here we show that a QC amino acid can be incorporated into a protein site-specifically using the pyrrolysine-based genetic code expansion platform, and subsequently used for ligation chemistry. Additionally, we exploited the photolability of the QC ligation product to render the adduct cleavable with a handheld UV lamp. We further developed a protein purification method that involves QC ligation of biotin to a protein of interest, capture on streptavidin resin, and finally release using only UV light. The QC ligation thus brings novel chemical manipulations to the realm of bioorthogonal chemistry.

SUBMITTER: Tomlin FM

PROVIDER: S-EPMC6170726 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Site-specific incorporation of quadricyclane into a protein and photocleavage of the quadricyclane ligation adduct.

Tomlin Frederick M FM Gordon Chelsea G CG Han Yisu Y Wu Taia S TS Sletten Ellen M EM Bertozzi Carolyn R CR

Bioorganic & medicinal chemistry 20180404 19

The quadricyclane (QC) ligation is a bioorthogonal reaction between a quadricyclane moiety and a nickel bis(dithiolene) derivative. Here we show that a QC amino acid can be incorporated into a protein site-specifically using the pyrrolysine-based genetic code expansion platform, and subsequently used for ligation chemistry. Additionally, we exploited the photolability of the QC ligation product to render the adduct cleavable with a handheld UV lamp. We further developed a protein purification me ...[more]

PMID: 29754834

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