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Positive or partial positive charges (electron withdrawing functional groups) stabilize the thiolate or the leaving group and, hence, catalyze the reactions, while negative charges have opposite effects

The HFI series of compounds, e.g., 37 (HFI 419) identified in 2008 after the virtual screening are much more drug-like than the hexapeptides 11 (AL-11), 12 (IVDE77), and the potent macrocyclic Ang IV analogue 23 (HA08) and can hopefully after further systematic optimization be converted into bioactive small molecules with capacity to cross the blood-brain barrier

the resultant APC, APR, exhibited enhanced degradation activity in breast cancer cells, albeit with the constraint of modest drug loading inherent to direct conjugation [234]

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