Abstract

Biocompatible chemical protein cleavage methods have been long-sought to replace enzymatic cleavages, but have yet to be realized. Here, we report the development of the SNAC-tag (Sequence-specific Nickel Assisted Cleavage) to achieve sequence-specific chemical protein cleavage under biocompatible conditions with comparable efficiency to enzymes. We demonstrate that the SNAC-tag can be inserted before both water-soluble and membrane proteins to achieve fusion protein cleavage, even when enzymatic cleavages fail.

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