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The P1 position can bind hydrophilic residues, the P2 position can bind lipophilic residues to increase the stability of plasma tension, and the PABC moiety acts as a spacer between the Val-Cit moiety and the payload, limiting the steric position of the payload blocking, allowing cathepsin B to exhibit its full protease activity towards linkers attached to bulky payload molecules such as doxorubicin

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