Site-specific Incorporation of Quadricyclane into a Protein and Photocleavage of the Quadricyclane Ligation Adduct

Overview

Journal Bioorg Med Chem

Specialties Biochemistry
Chemistry

Date 2018 May 15

PMID 29754834

Citations 3

Authors

Frederick M Tomlin

Chelsea G Gordon

Yisu Han

Taia S Wu

Ellen M Sletten

Carolyn R Bertozzi

Affiliations

Soon will be listed here.

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.

Citing Articles

Engineering Pyrrolysine Systems for Genetic Code Expansion and Reprogramming.

Dunkelmann D, Chin J Chem Rev. 2024; 124(19):11008-11062.

PMID: 39235427 PMC: 11467909. DOI: 10.1021/acs.chemrev.4c00243.

Developing bioorthogonal probes to span a spectrum of reactivities.

Nguyen S, Prescher J Nat Rev Chem. 2021; 4:476-489.

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Non-canonical amino acid labeling in proteomics and biotechnology.

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