The use of natural chemical reporter groups in combination with catalyst-free bioorthogonal reactions may greatly simplify the process of studying and perturbing protein function in its native environment. Here we report a novel nitrile-reactive peptide, VTNQECCSIPM (CX10R7), selected from a cysteine-encoded peptide phage display library through phage-assisted interrogation of reactivity (PAIR) towards 2-cyanobenzothiazole (CBT). Fusion of CX10R7 to a model protein, ubiquitin, directs specific labeling with CBT probes. The reactivity and specificity of CX10R7 can be attributed to the “microenvironment” effect in which the residues surrounding the two cysteines may help stabilize the ligation product through noncovalent interactions. CX10R7 represents a new class of bioorthogonal reporter group that utilizes natural amino acids for sequence-specific chemoselective protein labeling.

Sequence-specific 2-cyanobenzothiazole ligation identified through phage-assisted interrogation of reactivity

251st National Meeting (2016)

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