Chemical modification of proteins by insertion of synthetic peptides using tandem protein trans-splicing.

Khoo, K K; Galleano, I; Gasparri, F; Wieneke, R; Harms, H; Poulsen, M H; Chua, H C; Wulf, M et al. · Nat Commun · 2020

basic_science · Level V

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Abstract

Manipulation of proteins by chemical modification is a powerful way to decipher their function. However, most ribosome-dependent and semi-synthetic methods have limitations in the number and type of modifications that can be introduced, especially in live cells. Here, we present an approach to incorporate single or multiple post-translational modifications or non-canonical amino acids into proteins expressed in eukaryotic cells. We insert synthetic peptides into GFP, Na<sub>V</sub>1.5 and P2X2 receptors via tandem protein trans-splicing using two orthogonal split intein pairs and validate our approach by investigating protein function. We anticipate the approach will overcome some drawbacks of existing protein enigineering methods.

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