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Figure 4.
Figure 4. Evolution of selected fragments into reversible
inhibitors of caspase-3. (A) SAR of the reversible (aldehyde)
inhibitors derived from the selected fragments shown in Figure
2A. (B) Superposition of caspase-3 modified with extender A and
the salicylic acid sulfonamide tethering hit (fragment A; gray)
and caspase-3 bound to an irreversible version (in which the
aldehyde was replaced with an arylacyloxymethyl ketone) of
compound 4 (salmon). The arrow indicates a minor structural
accommodation observed in the S4 region between the tether and
the rigidified inhibitor.
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