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Figure 1. (A) Heterocatenane synthesis. Threading of the linear p53 thioester peptide through the cyclic p53 peptide results in folding of a p53 heterodimer, forming a pseudorotaxane (center). This folding brings the termini of the linear peptide in close proximity. Native chemical ligation cyclizes the second ring, and creates a heterocatenane (bottom). (B) Protein threading vs. protein folding. Folding of the linear monomer, bearing a fluorophore, has two possible paths. First, self-association and dimerization can occur (left), resulting in the formation of a linear dimer, which will still be fluorescent. Second, threading through the cyclic peptide, bearing a quencher, could occur (right), resulting in the formation of a pseudorotaxane, which will result in quenched fluorescence.