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Among those, the tyrosine derivative 28 exhibited a Ki value of 4.1 nM and the corresponding analogue with a saturated double bond, compound 29 , a Ki value of 25 nM, demonstrating that a proper constrain of flexibility of the ring system, alternatively an electron density in the center of the lipophilic bridge between amino acid residues in positions 1 and 3 is favorable for affinity to IRAP (Figure 7)

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Since agonistic PDCs are internalized into these compartments, a selective release of payloads can be achieved by using pH-sensitive linkers

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